Romelu Lukaku, who scored five times against Young Boys during his time at Everton, will look to continue his impressive start to the season as he prepares to lead the attack line for Jose Mourinho's men with help from Rashford and Alexis Sanchez.
Meanwhile, Young Boys defeated Sion 3-0 in their last Swiss Super League encounter.
United will be wary of any complacency after they were shocked by Sevilla at Old Trafford back in March.
Manchester United have been forced to change the way they play in order to battle back from a poor start to the season, according to manager Jose Mourinho.
Manchester United will be without the services of defenders Phil Jones and Marcos Rojo for the game, while captain Antonio Valencia has not travelled with the squad, due to concerns over his knee problem.
History tells us that things may be more hard than expected for the away side tonight.
"In the Premier League and in the Champions League, away from home is always hard".
Their plastic pitch is sure to make things a bit more hard for United and with Diogo Dalot in for his first start for the club, United fans will be hoping for a smooth away win.
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"Teams are really good and everything is a challenge".
Mourinho's decline as a Champions League force mirrors the fading challenge of United, who reached three finals in four seasons from 2008 but have struggled to make an impact since.
"We've won two games in a row - two tough away games - so we are confident".
"If I am sitting there as Marcus Rashford and someone says to me, 'Do you think your manager believes in you as his main, best striker and that he will build his team around you?' I would say, 'No".
United will face Young Boys on an artificial surface in Bern.
And on the importance of kicking off with a victory in Group H, De Gea added: "Especially in this competition, the first game is always very important to win".
"I don't think it's too far Mourinho's fault and too far Rashford's fault".
Instead of training at Carrington the day before the game, the players will train at the stadium on Tuesday evening in a bid to get used to the artificial pitch.