Saints will go to the top of the group with a win in the Czech capital and you can watch it for free.
When Southampton cruised past Sparta Prague 3-0 during the first round of Group K matches, they may have thought it unlikely that they would go into the return fixture two points behind the Czech side.
That is exactly the situation ahead of this evening's rematch, however, as Sparta's three straight wins have taken them top of the group.
If Southampton avoid defeat it will leave their fate in their own hands ahead of the final group match against Israeli club Hapoel Be'er Sheva at St Mary's.
The Key Battle - David Lafata versus Virgil van Dijk
Van Dijk's classy performances at the heart of Southampton's defence have reportedly caught the attention of the top clubs, and the Dutchman will be have to be on his game against the prolific Czech veteran whose goal tally has already reached double figures this season.
A Charlie Austin brace followed by a late strike from Jay Rodriguez secured a 3-0 win for Saints in September's clash between these two sides.
Recent form (all competitions) – most recent last:
Sparta Prague - WLWWDW
Southampton - DWLWLD
Who’s the ref?
Spaniard Jesus Gil Martinez - who also took charge of Manchester United's defeat at Feyenoord in September - will oversee this one.
He has shown four red cards and 57 yellows in his 10 matches so far this season.
What time is kick off?
The game begins at 6pm.
Where can I watch it?
BT Sport 3 are showing this one, while it is also available on free-to-air via BT Sport Showcase (Freeview channel 59, Sky 414, Virgin Media 548).
Sparta Prague - 3/1
Draw - 23/10
Southampton - 21/20