The San Francisco 49ers have barely had time to enjoy their 2-0 start before another injury hits their defensive front. After losing several players already this season, San Francisco now has to deal with a potentially lengthy absence of its biggest name up front: Nick Bosa.
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Five-time Pro Bowl defensive end Nick Bosa suffered a calf injury during practice this week and is expected to miss a few weeks, according to ESPN’s Adam Schefter. Bosa is already ruled out for Sunday’s game against the Arizona Cardinals.
“The 49ers now are leaning toward not placing DE Nick Bosa on injured reserve in part because they’re running out of injured reserve spaces, per source,” Schefter reported on Friday.
An IR move would force Bosa to miss at least four games. That would keep him out against Arizona, Denver, Seattle and Washington, although the 49ers are reportedly leaning toward keeping him off the list because of their limited number of designated return spots.
San Francisco can only designate eight players on injured reserve to return during the season. With the 49ers already carrying 15 players on that long list, that decision has become more complicated than simply placing Bosa on IR and waiting for him to heal.
Defensive tackles C.J. West and Alfred Collins, along with defensive end Sam Okuayinonu, are on injured reserve. And Andrew Farmer II and Mikail Kamara are also unavailable for the season.
Rookie defensive tackle James Thompson Jr. is dealing with a high ankle sprain, and Romello Height has been working through a broken hand. Mykel Williams, meanwhile, remains on the physically unable to perform list while recovering from the ACL injury that ended his 2025 season.
However, Williams is expected to begin practicing next week and could be eligible to return in Week 5. But that does little to solve San Francisco’s immediate problem.
In Bosa’s absence, Keion White, Khalid Kareem, and Ogbo Okoronkwo are among the defensive ends available to the 49ers. The team also added Naquan Jones and Viliami Fehoko Jr. to the practice squad this week.
For a defense built around Bosa’s ability to pressure quarterbacks, his absence changes the equation.
Bosa had only recently completed his comeback from another major injury. He tore his ACL in Week 3 last season against the Cardinals and missed the rest of the 2025 campaign. He worked his way back in time for the 2026 opener and has started both games, recording seven tackles, two tackles for loss, and one quarterback hit.
However, the timing has naturally brought another Bosa back into the conversation.
Could Joey Bosa Become an Option?
Joey Bosa remains a free agent after spending the 2025 season with the Buffalo Bills. He has 77 career sacks and five Pro Bowl selections, but there has been uncertainty over whether the 31-year-old intends to continue playing.
49ers’ reporter Akash Anavarathan suggested the team should consider contacting Joey because of its shortage of healthy edge rushers.
“Have to wonder if the #49ers are going to call Joey Bosa, as they desperately need EDGE rushers,” he wrote. “Not sure how long Nick Bosa’s going to be out.”
That is speculation, however, and there has been no report that San Francisco has contacted him. Adam Schefter previously reported that Joey could be nearing the end of his playing career, while Nick Bosa also expressed doubt during the offseason about his brother returning.
For now, San Francisco has a more immediate concern. The 49ers are 2-0, but their defensive front is being tested early, and losing Nick Bosa for several weeks only makes that challenge tougher.