McNeill, a two-time Pro Bowl pick, was injured during a collision with Raiders linebacker Aaron Curry while attempting to block on Ryan Mathews run. It appeared the taller McNeill was hit in the facemask by the top of Curry's helmet, then struck the back of his helmet on the ground when he fell to the turf.
McNeill was carted off the field and replaced by Brandyn Dombrowski.
San Diego's injury woes didn't stop with McNeill. Veteran linebacker Takeo Spikes sustained a concussion during the first half and was ruled out, and guard Louis Vasquez suffered an ankle injury and was considered doubtful to return.
NFL.com senior writer Steve Wyche also reported that defensive back Marcus Gilchrist walked to the locker room with a left hamstring injury and later was ruled out of the game.
The Associated Press contributed to this report.