The demonstrate, due to take place on August 25, will instead be at the nearby Cardiff International Arena. Tickets are still valid, but fans can get a refund if they wish.
About 18,000 tickets had already been sold for the stadium, against a capacity for the show of about 35,000.
Bob Gold, the band's European manager, told the BBC sales had not met expectations and it was decided it was punter for the band and the audience to move into "a smaller, more intimate venue".
Fans world Health Organization have already bought tickets have been contacted about the change.
They can function their stadium tickets, or get a refund, and have been offered discounts on other REM shows at Twickenham and Southampton.
Gold blamed the general economic situation for the deficiency of gross sales, although he said tickets for REM's other UK shows were "satisfactory".
REM play four shows on the second leg of their European turn, having already played a headline one-armed bandit at the T In The Park festival in Scotland last month (July 13).
The dates are:
Manchester Lancashire County Cricket Club (August 24)
Cardiff International Arena (25)
Southampton Rose Bowl (27)
London Twickenham Stadium (30)
To check the availability of REM tickets and get all the latest listings, go to NME.COM/GIGS now, or call 0871 230 1094.
Aug 24, 2008 at Lancashire County Cricket Club, Manchester -
Aug 25, 2008 at Millennium Stadium, Cardiff -
Aug 27, 2008 at The Rose Bowl, Southampton -
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