Tyldesley, who plays Weatherfield's Eva Price, has already pulled out of appearing on ITV's breakfast show Lorraine this week due to illness.
Tyldesley announced on her Twitter today: "Absolutely gutted I'm missing the NTAs tonight. Just don't feel upto it. Will be resting in bed cheering my wonderful colleagues on!"
Meanwhile, Metcalfe - Mercedes McQueen in Channel 4's teen soap - will miss the ceremony due to tiredness, according to The Sun.
A source claimed: "Jen's a feisty girl and wouldn't normally shy away from them. But she's emotionally exhausted and wanted a break before returning to Hollyoaks."
Neither Tyldesley nor Metcalfe have been nominated for a gong this year.
The National Television Awards, hosted by Dermot O'Leary, airs tonight from 7.30pm on ITV.
> National Television Awards 2013 - Nominations in full
> 'Emmerdale' deserves NTA success, says Fiona Wade