Donnelly and the Sky Sports News presenter ended their two-year relationship last month.
After the Geordie TV presenter joked that Cowell wasn't taking part in this year's UK X Factor because he "couldn't be bothered", the Syco boss took revenge by teasing him about his love life.
"Any change in your life... recently?" laughed Cowell. His comment brought laughter from an audience of journalists and Dec's best friend and Britain's Got Talent co-star Ant McPartlin.
Cowell and Ant & Dec were speaking at the launch of their new ITV1 gameshow Red or Black?. The game of luck, which offers punters a prize of £1 million, will take place at Wembley in the summer.
UK residents wanting to take part in the gameshow can apply now at www.itv.com/redorblack.
> Declan Donnelly split 'total shock to Thompson'