Wasps captain John Hart has learned he will be out for up to four months while lock Ross Filipo will be out for the rest of the season.
Number eight Hart, 29, suffered torn knee ligaments in last week's European Challenge Cup win over Bayonne.
Filipo, 32, has received surgery on a shoulder injury and is not expected to return before the end of the season.
Wasps have already lost James Cannon, Joe Launchbury, Billy Vunipola and Tom Rees to long-term injuries.
Hart has played 14 times this season while former All Black Filipo has made 12 starts and scored two tries since arriving at Adams Park in the summer.