Sykes’ television career stalled for a period, although she made a successful comeback as host of Today with Des and Mel with Des O’Connor in 2003. On 12 May 2006, ITV announced that the show would be one of a number to be axed in a “painful, but utterly necessary” move.
Sykes’ other work for ITV has included hosting shows The Vault (2003–2004), Celebrities Under Pressure and The British Soap Awards
Sykes appeared as a guest panellist on Loose Women in October and November 2005 and later returned as a guest anchor in October 2008 and May 2009.
From 2006 to 2009, Sykes regularly filled in for Paul O’Grady as presenter of The Paul O’Grady Show when O’Grady was unable to appear. She presented the show on eleven occasions.
Sykes was the presenter of the daytime series Gene Detectives for BBC One. In 2008, Sykes was a judge on ‘The Sofa Factor’, an item for GMTV, where viewers sent in short clips and the winner got to present TV Pick of the Day and win a trip to Las Vegas.