In a statement released by the team Saturday, coach Doug Marrone said the first-round draft pick would have a "minor knee procedure."
It's unclear when or how Manuel was hurt in the 20-16 win over Minnesota. He took over to start the second half and opened with a 14-play, 80-yard drive capped by a 4-yard touchdown pass to Brad Smith. He finished 10 of 12 for 92 yards in three series.
"EJ Manuel had some swelling in his left knee this morning and was examined by our medical staff," Marrone said. "An MRI revealed that he will need to have a minor knee procedure and that has been scheduled. He will miss the remainder of the preseason and then be re-evaluated at that time."
Through two games this preseason, Manuel completed 26 of 33 passes for 199 yards and two touchdowns, and ran four times for 29 yards.
Manuel was the first quarterback selected in the draft when the Bills chose him 16th overall out of Florida State.
Kolb will now start against Washington on next Saturday. Kolb was 13 of 21 for 111 yards and an interception on Sunday. Washington State rookie Jeff Tuel is the third-string quarterback.
Kolb signed with the Bills in the offseason after starting 21 of 32 career games played in a six-year career with Philadelphia and Arizona. He's thrown for 28 touchdowns and 25 interceptions while being sacked 77 times in a career that started as a 2nd round draft pick of the Eagles in 2007.
Marrone also says backup receiver Kevin Elliott will miss the season after tearing a ligament in his left knee.
The Bills return to the practice field at St. John Fisher College in Pittsford, N.Y. at 8 a.m. Monday. Marrone will meet with the media after practice.
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