May has failed to shine in wins over Wales and Italy and makes way for Nowell, who featured in all five matches during last season's tournament and has been in sparkling form for his club Exeter.
With fullback Mike Brown working through his return-to-play protocol after suffering a concussion in the victory over Italy at Twickenham on Feb. 14, England retained Alex Goode and Chris Pennell, back in the fold for the first time since the tour to New Zealand last June.
Brown completed a running session on Tuesday and could take part in non-contact training with the squad on Wednesday.
“Preparation has gone well and we’ve had a good build up so far. The guys who played against Wales and Italy did really well and the good thing is that others who are now fit and training are pushing hard for selection," coach Stuart Lancaster said.
“We’ve had to make some tough decisions but it’s a good position to be in and those players going back to their clubs have another big weekend ahead to lay down a marker for later in the tournament.
“Chris Pennell is in camp for the first time since last summer so we are taking this opportunity for him to spend some additional time with us."
Bath tighthead prop Henry Thomas will join training following a hip flexor strain to Kieran Brookes.
(Writing by Justin Palmer; editing by Toby Davis)
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