The boss managed Benfica - Portuguese champions and top Group A seeds - in the 2000/01 campaign in a short-lived tenure at the Estadio da Luz.
Having acted as assistant manager at Porto and Barcelona to Sir Bobby Robson and then a certain Louis van Gaal, Mourinho filled the same role at the Portuguese giants until he replaced the sacked Jupp Heynckes.
Jose's reign was only to last eleven games, though, and he quit after two months in charge after a raft of changes at boardroom level.
Reds midfield man Nemanja Matic played 73 times for Benfica across three seasons, and Swedish centre-back Victor Lindelof also makes his return to the club he signed for United from in the summer.
United are unbeaten both domestically and in Europe, and sit impressively in pole position in the group with two wins from two - and an extension of that record would see us all but seal a place in the knockout stages.
Benfica, by contrast, have lost both of their opening matches despite their status as, on paper at least, the strongest team in the group.
They sit third in the Portuguese SuperLig table after eight games, behind arch rivals Sporting and Porto, five points off the pace after five wins, two draws and a defeat so far.
A surprise 2-1 reverse to CSKA Moscow was followed up last time out by even more a shock as they were thrashed 5-0 at Basel.
The boss admitted that he's short of options for the trip with Michael Carrick, Marouane Fellaini, Paul Pogba, Eric Bailly and Zlatan Ibrahimovic all out.
Marcos Rojo and Luke Shaw, however, have travelled with the squad but this match is expected to come too soon for both.
Benfica full-back Andrea Almeida will miss out through suspension but Rui Vitoria has an otherwise full squad of players to pick from.
Jose said: "Our goal of course is to qualify, I think that one point away against the strongest of the three teams is a good result.
"Our sole objective is to qualify within that context, but it is a match that we also want to try and win.
"I believe it is hard for Benfica to qualify, but they need to make a point without question and I'm sure that Rui has done many different things in the Champions League - I have studied and analysed Benfica as best I can, that Rui has done many different things in the Champions League."
Form guide: Benfica D D W L D W United W W W W W D
Match odds: Benfica 7/2 Draw 13/5 United 5/6
Referee: Felix Zwayer (Germany)