The 49ers placed Pashos on injured reserve a day after he had an MRI exam on the shoulder. The veteran offensive lineman was hurt during Sunday's 24-21 loss at Houston, his first start at right tackle in place of Adam Snyder.
Coach Mike Singletary had hoped making Pashos the regular right tackle would help improve things on the line, where blocking and quarterback protection has been a problem. Pashos had been sharing right tackle duties with Snyder, who moved into a shared role at right guard with Chilo Rachal.
Singletary has called the line his biggest concern. San Francisco (3-3) plays at Indianapolis on Sunday with newly promoted quarterback Alex Smith set to start. The 49ers have lost two in a row following a 3-1 start.
Linebacker Takeo Spikes is nursing a strained right shoulder and was listed as day to day after undergoing an MRI on Monday.
When Singletary addressed the media Monday, he didn't want to speculate about how the line would look come Sunday if Pashos was out. But moving Snyder back to right tackle and keeping Rachal at right guard seems like the most logical move.
"Right now, we have to continue to help Chilo as much as we can," Singletary said. "I think one of the issues we have right now, some guys are really trying to play perfect. Some guys are really trying to play mistake-free. When you do that, you become robotic and it takes you out of your game. I just want guys to go out and play."
The 29-year-old Pashos, a seventh-year veteran, signed with San Francisco on Sept. 7 after being cut by the Jaguars. He played two seasons with the Jaguars after spending his first four years in the NFL with Baltimore.
In addition Tuesday, the Niners released linebacker Marques Harris and promoted linebacker Diyral Briggs from the practice squad to the active roster.