Manchester City prepare to face Paris St Germain on Wednesday as the former team booked their place in the knockout phase with a composed 2-0 win at Schalke 04 last time out, but the Germans can join the Premier League side if they win at FC Twente.
Paris St Germain travel to City's Eastlands ground, and despite a recent revival in their league form they are desperate for UEFA Cup points after a draw and a defeat in their first two games left them bottom of Group A.
Meanwhile Portsmouth go into their third UEFA Cup group stage game at German side Wolfsburg on Thursday knowing that only a victory will keep their destiny in their own hands.
Roared on by a raucous home crowd against favourites AC Milan in their last match in the competition, Portsmouth went two goals up before conceding twice in the game's dying stages to draw 2-2.
The result was enough to send the Italian giants through, but Pompey now sit fourth in Group E with only one point to their name.
With only the top three sides going through, a draw for Wolfsburg will secure their progress and give Portuguese side Braga the chance to join them in the next round if they win at Dutch outfit Heerenveen.
Pompey, though, will be boosted by the return to fitness of leading scorer Jermain Defoe, who was forced to sit out the Milan match with a calf problem.
He returned to partner Peter Crouch in a 3-2 league victory over Blackburn Rovers at the weekend and Crouch says his team-mates are thinking only of victory in Germany.
“I'm sure there is still a chance for us and while that's the case we'll go for it,” he said. “A win on Thursday leaves it wide open.”
The situation facing Portsmouth's Premier League counterparts Aston Villa is an altogether rosier one, with the Birmingham side needing just a point at home to Zilina to progress.
Martin O'Neill's men did not play in the last round of matches, but they stayed top of Group F on goal difference ahead of Ajax, who won 1-0 at Hamburg.
Villa were held to a frustrating 0-0 draw at home to Fulham on Saturday, but O'Neill flatly rejected accusations they were feeling under pressure.
“As regards choking, I do not accept that. Every game is hard and we are not brilliant enough at the moment to steamroll teams but we are doing fine,” he said.
A win for Villa against the Slovakians would mean Martin Jol's Hamburg will also go through if they win against Czech side Slavia Prague.
The 2006 and 2007 UEFA Cup winners Sevilla have slipped off the pace in Group C as they prepare to host already-eliminated Partizan Belgrade on Wednesday.
Belgium's Standard Liege top the group on six points, two points clear of Stuttgart and Sampdoria and three points clear of fourth-placed Sevilla.
Standard host Sampdoria on Wednesday night, with both sides knowing victory would probably be enough to seal their qualification.
With two rounds left to play in the group phase, only AC Milan, Manchester City, CSKA Moscow and Saint Etienne are through, with 36 teams still in with a chance of joining them.
UEFA Cup fixtures
Wednesday (1945GMT unless stated)
Manchester City v Paris St Germain, FC Twente v Schalke 04, Metalist Kharkiv v Olympiakos, Hertha Berlin v Galatasaray, Standard Liege v Sampdoria, Sevilla v Partizan Belgrade, Spartak Moscow v NAC Breda (1700GMT), Udinese v Dinamo Zagreb (1700GMT)
Thursday (1945GMT unless stated)
Wolfsburg v Portsmouth, Heerenveen v Braga, Slavia Prague v Hamburg, Aston Villa v Zilina, Valencia v Club Brugge, FC Copenhagen v Rosenborg, Lech Poznan v Deportivo La Cornua, Nancy v CSKA Moscow
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