Spiller injured his ankle in Sunday's win against the Ravens and was seen limping in the locker room as late as Tuesday.
It is not immediately clear if McKelvin being active means that Aaron Williams, who has played cornerback since McKelvin's injury, will return to safety.
Offensive lineman Sam Young is inactive for the first time this season, as top backup lineman Doug Legursky is active for the first time this season. Legursky suffered a knee injury in the preseason finale.
Full list of Bills inactives:
S Jairus Byrd
OL Sam Young
TE Chris Gragg
CB Ron Brooks