Their Adams Park clash against Bath presents another difficult hurdle to overcome on the back of their draw at Bristol.
Wasps rugby director Ian McGeechan said: "Bath have been playing some outstanding rugby this season, and consequently they are the form side in the Premiership at the moment.
"We know that, due to our poor start to the season, we are in catch-up mode - and for Wasps, this game is without doubt the biggest challenge of the season to date."
Lawrence Dallaglio returns to captain Wasps, after being rested for the Bristol trip - while full-back Mark Van Gisbergen, whose defensive howlers 'gifted' Bristol two tries, is on the bench.
Leicester hand rare first-team starts to the likes of prop Boris Stankovich, hooker Mefin Davies and fly-half Ian Humphreys for the Welford Road appointment with London Irish.
Injuries are taking a toll on the Tigers - with Lewis Moody, Marcos Ayerza and Geordan Murphy among those absent - and Leicester head coach Marcelo Loffreda acknowledged: "It is going to be a very hard game.
"We have made some changes to the team but we have a lot of confidence in our squad and we trust the players that will play."
Irish, who could climb above Bristol into seventh place if they win, make just one change following victory over struggling Worcester last time out - scrum-half Paul Hodgson replacing Peter Richards.
Exiles rugby director Brian Smith said: "We got our Premiership season back on track last Sunday when the players held their nerve in very difficult conditions against a rapidly-improving Worcester team.
"We will be asking the players for another big performance tomorrow (Saturday) against a team that are as formidable as any we are likely to meet in this country or in Europe."
Worcester, still bottom despite claiming a losing bonus point at Irish, can climb off the basement by beating Sixways visitors Harlequins - while Sunday's action sees Saracens hosting Newcastle and Leeds Carnegie at home to Sale Sharks.