Nick Bosa’s Injury Curse Strikes Again: 49ers Star Out Multiple Weeks With Calf Strain

Nick Bosa’s nightmare injury luck has struck again. The San Francisco 49ers star pass rusher suffered a calf injury during Thursday’s practice and is expected to miss “a few weeks,” according to ESPN’s Adam Schefter and NFL Network’s Ian Rapoport, ruling him out of Sunday’s showdown with the Arizona Cardinals. The news sent Bosa’s name rocketing up Google Trends and social media Friday, just as the five-time Pro Bowler was finally rounding back into form.

Bosa, 28, tore his right ACL against these same Cardinals in Week 3 last season, an injury that limited him to just three games in 2025. He worked his way back through a full offseason of rehab and looked sharp in San Francisco’s first two games of 2026, logging seven tackles, including two for loss, across 70 snaps in wins over the Rams and Dolphins. The 49ers were counting on their $34 million-a-year edge rusher to anchor a defense that recorded an NFL-worst 20 sacks a year ago, and bettors weighing DraftKings promo code offers for NFL Sunday slates will want to factor his absence into any Cardinals-49ers lines.

A Defensive Line in Freefall

Bosa’s calf strain is merely the latest blow to a San Francisco front that defensive tackle Osa Odighizuwa this week bluntly labeled a “horror show.” Over the past two weeks alone, the Niners have lost defensive tackle Alfred Collins to a season-ending torn patellar tendon, defensive end Sam Okuayinonu to a broken foot, defensive tackle C.J. West to a chipped knee bone that landed him on injured reserve, and rookie James Thompson Jr. to a high ankle sprain expected to sideline him three to six weeks. Rookie edge rusher Romello Height is also nursing a broken hand, though he has an outside chance to suit up Sunday.

That leaves San Francisco with Keion White, Khalid Kareem and Ogbo Okoronkwo as the only healthy, available defensive ends heading into a critical NFC West matchup at Levi’s Stadium. Head coach Kyle Shanahan acknowledged the depth crunch this week, noting the team is weighing whether to place Bosa on injured reserve, which would sideline him a minimum of four games and make him eligible to return for an Oct. 25 trip to Atlanta. According to reports, the 49ers are currently leaning against the IR move in part because they are running low on return slots after already committing several roster spots to other injured linemen.

How the News Broke

The first signs of trouble surfaced Wednesday, when Bosa was held out of practice with what was initially labeled a “resting player/knee” designation. Thursday brought a calf issue added to the report, and the 49ers notably delayed releasing their injury report for hours that evening — an unusual move that fueled speculation before Friday’s official word. NBC Sports Bay Area’s Jennifer Lee Chan flagged the delay as an ominous signal in real time, telling her audience to “prepare yourself mentally” for bad news, a read that proved accurate less than 24 hours later.

For a defense already stretched thin, losing Bosa is a considerably bigger blow than the line injuries that preceded it. He remains one of the league’s premier disruptors, with 64.5 career sacks, 13 forced fumbles and 285 tackles across 87 games since San Francisco drafted him second overall in 2019. His absence Sunday also carries an eerie symmetry: it comes almost exactly one year after he tore his ACL against this very same Cardinals team in the same building.

What It Means Going Forward

At 2-0, San Francisco still holds sole possession of first place in the NFC West, but the margin for error narrows considerably without its best pass rusher. Arizona enters Sunday at 1-1 and will look to exploit a suddenly thin front seven that no longer features the player who tormented quarterbacks for much of the past six seasons. Whether Bosa ultimately lands on IR or manages to return within a few weeks, the 49ers now face the challenge of generating pressure with a patchwork rotation for at least the immediate future — a storyline that will shape how the rest of the NFC West race, and San Francisco’s playoff positioning, plays out over the coming month.