Lewsey and several of his England colleagues will line up at the Millennium Stadium just a week after suffering their Calcutta Cup humbling at Murrayfield.
But any notion England's players might be suffering an extended hangover in terms of feeling sorry for themselves following events in the Scottish capital will be dismissed when the Anglo-Welsh Cup semi-finals swing into action.
Leicester and Wasps are first up, followed by Bath tackling Llanelli Scarlets with the prize of an April 9 Twickenham final at stake.
Wasps were mauled twice by the Tigers in European Cup combat last season, before gaining revenge during a one-sided Premiership final when Lewsey and company completed a league title hat-trick.
The tie throws up numerous intriguing individual battles - most notably between England number eight rivals Martin Corry and Lawrence Dallaglio - and red rose supremo Andy Robinson will be a keen observer eight days before the world champions face France in Paris.
"It is a strong rivalry to say the least, and it is difficult to put it into words," said Wasps back Lewsey.
"I was quoted before as saying that they (Leicester) know us inside-out and we know them. There have been so many games over the past two years where we've got to know each other a little bit more.
"When you lose to someone you know so well it is like losing to your brother in the back garden. It hurts more than anything, because there are bragging rights at stake.
"When you beat your main rival you feel a couple of inches taller especially when you meet up with the England camp. You feel as if you can go in there with your head held high, so the rivalry is very much alive.
"In both of those Heineken Cup games last season, we gifted Leicester soft scores in the first 20 minutes," Lewsey added.
"You cannot afford to do that against quality teams because you will always have to play catch-up."
Leicester head coach Pat Howard expects to field most of his current international crop, although England scrum-half Harry Ellis has missed out on a starting place, with Austin Healey handed the number nine shirt.
"Harry has been playing very well for club and country, but Austin has been in great form and I wanted to reward him in a competition he has been integral to," said Howard.
"There is a very positive vibe around the club, and this is a big game against Wasps. We are at the business end of the season now, and we know there is pressure, but that's great.
"We are in a good position, and we just have to keep fighting and peak for the big games when there are no second chances if you lose."
Bath are set to be without injured backs Olly Barkley, David Bory and Michael Stephenson against the Scarlets, but England prop Matt Stevens could return after missing the Scotland Six Nations defeat because of a shoulder problem.
Llanelli's sizeable Welsh international contingent are all available apart from scrum-half Dwayne Peel, who has not been released by Wales caretaker coach Scott Johnson, for a semi-final that could prove even closer than the Leicester versus Wasps tie.
"Bath's coaching set-up has changed, they have done well in their last few games and they will want to get to the final at Twickenham," said Scarlets back-row forward Alix Popham.
"This game is massive for us. We are out of the Heineken Cup, but we are still in with a shout in the Celtic League and the Powergen Cup, so there is a chance of some silverware this season."