Giggs' next United appearance will be his 900th, but it was always likely that after playing such an impressive part in his club's Premier League title charge, he would be excused a last-32 first-leg meeting with Ajax.
It was anticipated Berbatov and Evra would be involved, although with no official injury update, the reason for their absences is not likely to become known until a later press conference.
There was good news on the injury front though as Nani and Phil Jones both returned after recent absence
In addition, Ashley Young and Tom Cleverley were named in a 20-man squad, along with youngsters Paul Pogba and Zeki Fryers.
Thursday's game will be the first time United have competed in a European match outside the Champions League since 1995, when they were beaten on away goals by Russian outfit Rotor Volgograd in a UEFA Cup first round tie.
However, whilst it might mean a Thursday night debut, a meeting with Ajax does sound like a Champions League game.
Striker Javier Hernandez accepts the Red Devils would have preferred to be in the main UEFA competition this week.
However, if they are to make their Europa League bow, there are few more famous names to do it against than the Dutch giants, who with four European Cups to their name have one more than the Red Devils.
"Both teams have come out of the Champions League and they both have a great history," said Hernandez.
"We have won a lot of European Cups between us, so it will be a very interesting game.
"We need to get used to the fact we are not in the Champions League this season.
"And the history of Manchester United is such that it doesn't matter which competition you are in, we want to win it, no matter who else is in it or whether it is an important trophy for other teams."