Sale, who will have to sit out a minimum of 10 days under MLB protocols, was scheduled to start against the Chicago White Sox on Sunday.
"It's unfortunate, but he'll be back,'' manager Alex Cora said before Friday night's 4-3 loss to the White Sox in the series opener. "He feels good. He actually feels great, and hopefully he can come back right away, right after his X amount of days.''
The team on Saturday announced that utilityman Danny Santana had been placed back on the COVID-19 injured list, just four days after coming off of it. The Red Sox recalled infielder Jack Lopez from Triple-A Worcester to fill Santana's spot on the active roster.
Sale joins a growing list of Boston players since Aug. 27 to test positive for COVID-19, with others sidelined because of symptoms or close contact with positive cases. Nine players -- including Santana, shortstop Xander Bogaerts, reliever Matt Barnes and starter Nick Pivetta -- are the most recent to be on the team's COVID-19 injured list.
Bogaerts was reinstated Friday and returned to the starting lineup against the White Sox. But designated hitter J.D. Martinez was scratched because of back spasms.
It was Bogaerts' first game since he was pulled from an 8-5 loss at Tampa Bay on Aug. 31 after the Red Sox found out he had tested positive. The three-time All-Star had to stay behind in Florida after the team departed.
Bogaerts said he felt fine the whole time.
"It was boring, man,'' he said. "I wouldn't want that for anyone. At least if you're in Boston you're at home."
Cora said Pivetta is feeling good after his injured list stint and is in line to start in Sale's place on Sunday. Right-hander Connor Seabold is on the team's taxi squad for the road trip and will start Saturday in his big league debut.
Left-hander Darwinzon Hernandez was activated from the 10-day injured list Friday after being sidelined by a right oblique strain, and right-hander Kaleb Ort was promoted from Triple-A Worcester. Hernandez pitched 1⅓ scoreless innings in the loss to the White Sox.
The Red Sox also placed infielder Jonathan Arauz on the COVID-19 injured list on Friday, and lefty Austin Davis went on paternity leave. The move with Arauz is precautionary; he has some symptoms, but he has tested negative multiple times, according to the team.
"It's not easy," Cora said. "It's actually very hard. But this is our reality. We have to keep going."
Sale, a seven-time All-Star, missed the 2020 season recovering from Tommy John surgery. Since rejoining the rotation, Sale has looked like his old self, going 3-0 with a 2.52 ERA in 25 innings across five starts.
ESPN's Jesse Rogers and The Associated Press contributed to this report.