Heskey, who is often the target of critics who feel his goalscoring record does not meet the required standard, will be hoping to lead the line alongside Wayne Rooney for his country in the World Cup finals this summer.
But O'Neill, who knows the 32-year-old well from their time together with Leicester, believes the amount of times he limps from the action could become a concern for Fabio Capello.
"It's been frustrating because he's had to come off with niggles," O'Neill admitted.
"If he wants to be a starting England player it's important he stays on the field.
"He's always seemed to have had niggles, even when he was a kid at Leicester.
"I remember him coming off in some matches there, important games too, maybe it's his make-up.
"Obviously a collection of injuries might force you off but you just have to be able to overcome them and play with a little bit of discomfort.
"I am not asking players to play in complete pain, but some players do, for most of the season, play in a bit of discomfort."
England Top Goalscorer England Top Scorer: Heskey, E 14/1