Including that three-game, mid-April sweep in St. Petersburg, the Red Sox -- who started 6-13 -- have since gone 27-16.
Still, Tampa Bay came to Boston a week later and returned the favor, sweeping the Red Sox in a rain-shortened two-game set.
Will this weekend bring another defining series? Before the Red Sox and Rays play four games in three days at Fenway Park, here's where the two teams stand.
1. The Red Sox have work to do
In five games against the Rays, no Red Sox starting pitcher has allowed more than three earned runs. Even in their two losses, Boston's starters were solid: David Price allowed two runs in his six innings, a strong effort in which the offense struggled to a 2-1 defeat; and Chris Sale survived a shaky first two frames to go seven innings in a 5-2 Rays victory.
Since the up-and-down first month of the season, Red Sox starters have bounced back. Boston's pitching staff as a whole entered last month with a 5.00 ERA but posted a 3.99 ERA in May, up from 25th to 12th in baseball. Sale went from a growing concern to his old ways again, striking out 66 hitters in 38⅓ innings pitched, with a 2.82 ERA. Price has been the most consistent pitcher on the staff over the entire season, with a 2.83 ERA and a 1.04 WHIP, and he carried it through a tough April.
But the Red Sox have had some issues elsewhere.
"Pitching, we're way close to who we are, although the results the first 10 or 11 days of the season, that wasn't us," manager Alex Cora said after last weekend's New York Yankees series, in which Boston lost two of three. "Defensively, we've been a lot better early in the season. Baserunning, the last 10 days have been sloppy. Offensively, although people don't see it that way, that's where we need to get better."
The defense has made strides in the field, most notably by Rafael Devers at third base. The 22-year-old misplayed several routine grounders in April but took a large step forward in May, improving his footwork considerably while making several spectacular plays moving to his left.
As for the offense, after sweeping the Kansas City Royals this week, Cora said the Red Sox are making progress, but they're still not quite where they need to be. Cora is looking to find more lefty-righty balance in his batting order.
"[Opponents] have to think about whether you bring out the specialist for the lefty or the righty because the lefty is right behind him."
The offensive production did look good against the Royals, as Boston scored 23 runs in three games in Kansas City -- but again, it was against the Royals, who have the second-highest staff ERA in baseball.
These are the Rays, who boast reigning AL Cy Young Award winner Blake Snell and the best pitching staff in baseball so far this season. While the Red Sox will miss Charlie Morton, who has posted a 2.30 ERA in 13 starts this season, they'll face off against Snell in the series finale. The 26-year-old lefty has a 3.22 ERA in eight starts against Boston in his career, but he has not faced the team yet this season.
2. The Rays have a new look -- again
The Rays change the foundation of their roster frequently and in often surprising ways. So far this season, Tampa Bay's two biggest offensive contributors have been outfielders Austin Meadows and Tommy Pham -- both of whom were playing for different teams at this point last year.
Meadows, who came to the Rays from the Pittsburgh Pirates in the Chris Archer trade, was taken by Pittsburgh with the ninth pick of the 2013 draft, two slots after Boston selected high school lefty Trey Ball, who has a 7.58 ERA in 34 relief appearances at Double-A Portland this season.
The 24-year-old played well in his debut last season in Pittsburgh, hitting .292/.327/.468 in 49 games there before the trade; but Meadows really has taken off at the plate this year, hitting .349/.424/.646 with a team-high 12 homers, 38 RBIs and 2.4 WAR, which has him tied for 16th in baseball.
Pham also has continued his strong performance with Tampa Bay, building off the momentum following his July trade from the St. Louis Cardinals, when he hit .343/.448/.622 with seven homers in 39 games with the Rays. It has been more of the same this season, as he is hitting .293/.406/.471 with eight homers, 25 RBIs, nine doubles and two triples.
Also worth keeping an eye on is rookie second baseman Brandon Lowe, who has impressed so far this season with a .272 average and 11 homers in 54 games and already is 3-for-10 with a homer against Boston.
For the Red Sox, rookie third baseman Michael Chavis faces the Rays for the third time after making his debut April 20 at Tampa Bay with a double off Jose Alvarado in his first MLB at-bat, setting up the winning run. Chavis, named the American League's Rookie of the Month for May after hitting seven homers, is going through his first prolonged slump in The Show, hitting .107 in his past seven games.
3. This weekend could shake up the AL East race
For the optimists who believe the Red Sox have underperformed so far this season, a sweep of the Rays would be a major step toward Boston eventually sitting atop the American League East.
The Red Sox enter the series five games behind the Rays, who themselves trail the first-place Yankees by a game and a half.
This weekend also gives Tampa Bay an opportunity to retake the division lead, while halting Boston's climb into contention.
And if neither club can catch the Yankees, Boston and Tampa Bay also could be on a collision course to meet in the winner-takes-all wild-card game.
For the Red Sox, a wild-card berth would significantly raise the level of difficulty in defending their World Series title -- but, say the pessimists out there, there's no guarantee they'll even get that far. The Red Sox enter the series in a virtual tie (they trail by a single percentage point) for the second wild-card slot with the Texas Rangers, who start a three-game series at Fenway on Monday.
When Boston last played Tampa Bay at the end of April, the Red Sox left the series six games under .500 and 7½ games out of first place. Fast forward nearly a month and a half later and Boston has climbed over .500. Yet they're in just about the same place they were in the division.
You'll often hear Cora and his players repeat, especially after a loss, that all wins and losses count the same, even if head-to-head matchups with division rivals carry significantly more emotional baggage. But as the trade deadline inches closer, the Red Sox will need to decide how much to stick with their current group of players and how much they'll need from the trade market. For one, closers such as Will Smith of the San Francisco Giants, Sean Doolittle of the Washington Nationals or Ken Giles of the Toronto Blue Jays could be options to add a lockdown arm to the current bullpen group after Craig Kimbrel departed as a free agent this past winter.
Cora already has started tweaking his lineup, and the results from this weekend -- against a potential wild-card opponent and a key division rival -- could dictate the kind of changes still to come.