Jose Mourinho knows Manchester United have already reached their own knockout stage of the Europa League.
United head into Thursday night's game at Old Trafford against Feyenoord with qualification for the last 32 hanging in the balance.
Mourinho's men currently sit third in Group A behind joint leaders Feyenoord and Fenerbahce and defeat is likely to prove fatal.
"It's simple - we need four points to qualify and it doesn't matter what happens in the matches where we are not involved," Mourinho said.
"There is no space for a defeat tomorrow, because (it is) a game where we have only two options and the third option, defeat, (means) we are out.
"We are going to approach the game knowing it is a knockout game for us and we cannot lose."
Henrikh Mkhitaryan is set to get a rare chance to impress for United, while Luke Shaw is also ready to return for the first time since Mourinho questioned the England full-back's apparent unwillingness to play through the pain barrier at Swansea a fortnight ago.
Southampton are in better shape than United ahead of their trip to Group K leaders Sparta Prague, who lost 3-0 at St Mary's in September before replacing Zdenek Scasny with David Holoubek.
Should they win at the Generali Arena and Hapoel Be'er Sheva not defeat Inter Milan, the Saints' progress into the last 32 will be secured, even with one remaining fixture at home to the Israelis in December.
But Southampton captain Jose Fonte and Dusan Tadic have not travelled to Prague because of injuries, while £16million record signing Sofiane Boufal faces a late fitness test after a bout of illness.
"Jose had a pain in his foot. He made a tackle against Liverpool and he cannot play," Saints boss Claude Puel said.
"And also Dusan has a problem with his nose.
"For the moment it is a serious problem and I don't know if for the next game against Everton he can play with this but it is difficult."
Dundalk would put themselves on the brink of a last 32 place by beating Dutch visitors AZ Alkmaar.
The Irish minnows - the lowest ranked team in the tournament - are in second place on four points alongside Maccabi Tel Aviv, who make the trip to Russia to meet runaway Group D leaders Zenit St Petersburg.
AZ are two points further back and Dundalk boss Stephen Kenny said: "From our point of view, no one gave us a chance of getting a point in the group.
"We still have a lot to do to get through. But we've come from the bottom of our own league to win three in a row and now to be on the verge of qualifying for the last 32.
"We are very determined to achieve that."
Along with Zenit, Shakhtar Donetsk and Schalke are the only sides with 100 per cent records after four games and have already won their respective sections.
The clash between Gent and Sporting Braga could go a long way to determining who finishes second to Shakhtar in Group H, while Krasnodar are in pole position to beat Red Bull Salzburg and Nice to the runners-up spot behind Schalke.
Ajax could secure top spot in Group G at home to Panathinaikos and Roma would do the same in Group E by beating Viktoria Plzen, as would APOEL if they win at Group B's bottom-placed team Astana.
Group J leaders Fiorentina are at home to PAOK, but Qarabag have not given up the race for top spot as they head to Slovan Liberec.
The picture is a lot more complicated elsewhere with St Etienne and Anderlecht tied on eight points in Group C, with Mainz - who visit the French leaders - still in the running three points back.
In Group F, only one point separates top two Genk and Athletic Bilbao from Rapid Vienna and Sassuolo, while FC Zurich and Villarreal meet each other in Switzerland two points down on Group L leaders Osmanlispor, who are away to Steaua Bucharest on Thursday.
Source: PA-WIRE
