Chargers general manager Tom Telesco told radio station XTRA 1360 that the rookie defensive end is dealing with a "minor" hamstring injury and is unlikely to be available Sunday.
"Obviously, we're not optimistic right now," Telesco told the station. "It truly is a day-to-day injury. It's a minor hamstring, and our goal is to make sure it doesn't turn into something long term."
Bosa, the No. 3 overall selection in this year's NFL draft, missed all of training camp and the preseason while embroiled in a contract dispute with the club. He finally ended the 31-day stalemate by signing a four-year contract worth a reported $26 million, including a $17 million signing bonus.
Bosa sustained the injury on Monday and hasn't practiced since. Telesco does not want to take any chances with a player expected to bolster a pass rush that ranked 24th in the league last season with 32 sacks.
"I know Joey's desire to play is very, very high, but we need to be smart about it," Telesco said.