Starting cornerback Leodis McKelvin did not return after aggravating an ankle injury in the first half. Also unable to finish were starting safeties Donte Whitner, who hurt his thumb, and Bryan Scott, who also hurt his ankle in the second half. Starting left tackle Demetrius Bell left the game after sustaining a groin injury.
Without providing details, coach Dick Jauron would only say the players were being evaluated.
McKelvin, who left the game midway through the first half, had already been bothered by a sore ankle which he hurt in last week's 33-20 win over Tampa Bay. The prevented him from handling kickoff returns against the Saints.
Bell did not return after he was hurt in the fourth quarter and was replaced by veteran backup Kirk Chambers. The Bills' offensive line is already depleted after losing starting right tackle Brad Butler to a season-ending knee injury last week.
Saints coach Sean Payton said running back Pierre Thomas missed the first half while being treated for flu-like symptoms. Thomas was well enough to play the second half and finished with a career-best 126 yards rushing and two touchdowns rushing, both scores coming in the final 10 minutes.