United crashed out of last year’s campaign after losing at Basel, a game in which captain Nemanja Vidic suffered a serious knee injury that ruled him out for the rest of the season.
The Old Trafford were finalists in three of the previous four years prior to their premature exit last time out but United only named the same back four twice out of 10 European matches last term.
“The key for us is if we can keep the defenders fit,” the Scot told reporters ahead of his side’s meeting with Galatasaray at Old Trafford on Wednesday night.
“I really mean that, because we’ve had a really rough ride with defenders being injured for the last two or three years.
“But if they remain fit, it definitely gives us a better opportunity, as we are particularly strong in the attacking part of the team, so hopefully that makes a difference to us.
“At the moment, with Chris Smalling and Phil Jones out long-term, I’m left with three fit centre-backs in Nemanja Vidic, Rio Ferdinand and Jonny Evans.
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“If I was guaranteed that two of those would be fit for the rest of the season, I’d take that gladly right now, but it’s not been the case in the last two or three years."
The 70-year-old admitted he was "careless" with his team selection at times last season and insisted he will be picking a full-strength line-up against Fatih Terim's side.
“We don’t want to be as careless as we were last season and the team I choose [against Galatasaray] will reflect that,” he added.
“I think we’d all agree we were careless in two of the games at home last season.
“Over the past few years the group stages have been very straightforward for us, so it gave me the opportunity to play a lot of young players.
“But I’ll be playing a more experienced team this time around.”