Mayo, the NFL's Defensive Rookie of the Year last season, was hurt after tackling running back Fred Jackson at the end of a 16-yard run.
Patriots coach Bill Belichick said on Monday that he did not think the injury was season-ending but did not offer further details.
The Bills lost two solid defensive players, linebacker Paul Posluszny and end Chris Kelsay, both in the third quarter. Posluszny, who had six tackles, broke his arm and there was no timetable for his return, coach Dick Jauron said.
"The doctors didn't give me a definite idea [how long I would be out], but they did say it will need surgery and then I'll go from there," Posluszny said, according to The Buffalo News. "But I should definitely be back. From what they told me, it's definitely not an IR thing."
Kelsay injured a knee. No details were announced.
Mayo led the Patriots in tackles last year after being drafted in the first round out of Tennessee. He took over defensive signal-calling duties late last season then became the team's leader at linebacker this season when Mike Vrabel was traded and Tedy Bruschi retired.
As a rookie in 2007, Posluszny suffered a season-ending broken forearm in the third game, also against the Patriots, who won 38-7. He was drafted in the second round from Penn State.
Information from The Associated Press was used in this report.