San Francisco 49ers running back Isaac Guerendo is dealing with a hamstring injury and is unlikely to play Sunday at the Miami Dolphins, a source told ESPN's Adam Schefter on Thursday.
Guerendo has risen to the top of a 49ers depth chart at the position that has been decimated by injury this season. Christian McCaffrey, Jordan Mason and Elijah Mitchell all sustained season-ending injuries this season.
Guerendo injured the hamstring against the Rams last week after he was questionable for that game because of a foot injury. He did not participate in Wednesday's practice.
The other running backs on the 49ers' 53-man roster are Patrick Taylor Jr. and Israel Abanikanda. Taylor is expected to get the first shot to replace Guerendo. The 49ers also have running back Ke'Shawn Vaughn on the practice squad, and he has been elevated the past two games with Abanikanda inactive.
Guerendo has rushed for 381 yards and four touchdowns this season.
The 49ers are also likely to again be without left tackle Trent Williams on Sunday. Williams has missed the 49ers' past four games with an ankle injury, and coach Kyle Shanahan said Wednesday that it's "getting closer" to the point where the three-time All-Pro will be sidelined for the rest of the season.
The 49ers (6-8) are mathematically alive for a playoff spot but likely need to win each of their three remaining games and get help to qualify.
ESPN's Nick Wagoner contributed to this report.