With a difficult trip to Turkey and hosting Manchester City at Anfield in an early kick off, selection could be key for Liverpool's chances of progress in Europe and a win against the champions.
It's another big week in Liverpool's season, with the Reds travelling to Turkey to a place that holds happy memories for them - the scene of their most remarkable European triumph 10 years ago.
But the Reds will be hoping there is no need for a comeback this time around as they take a 1-0 lead to Istanbul - where they take on Besiktas in the second leg of their last-32 Europa League tie.
Following on from their trip to Turkey, they have a lunchtime kick off against champions Manchester City at Anfield on Sunday - one of the hardest games Liverpool could wish for after two four-hour flights.
Like with Sunday's win at Southampton, there are bound to be changes for the side's exploits in Europe. Brendan Rodgers made three changes to the side that started at Anfield the previous Thursday by bringing in Lazar Markovic, Raheem Sterling and Dejan Lovren for Alberto Moreno, Daniel Sturridge and Mamadou Sakho.
Markovic is suspended for the game in Turkey, while Liverpool are likely to be without Steven Gerrard, Jose Enrique, Jon Flanagan and Jose Enrique, while Sakho will be a doubt after picking up a knock to the hip prior to the trip to the South Coast.
One of the main factors to consider will be the use of the forwards. All four of Sturridge, Mario Balotelli, Rickie Lambert and Fabio Borini didn't start the win over Southampton, so it would make sense for Rodgers to give Sterling a break. It could be the kind of game for Balotelli or Lambert to hold the ball high up the field as the Reds look to control proceedings and ensure a safe passage to the next stage of the competition - and it would make more sense for Sturridge to start the clash against his former club at Anfield three days later.
Emre Can and Philippe Coutinho could also be candidates for a rest - while Jordon Ibe potentially playing another game is a big factor in the 19-year-old's development. He has proved to be a big threat on the right for Rodgers's men but there is the issue of too many high profile games in such a short space of time.
And there is the issue of Jordan Henderson and Joe Allen starting alongside each other for five games on the bounce. It is hard to see Rodgers making too many changes to the Liverpool side.
One anticipates that Sturridge will be wrapped up in cotton wool, and there could be a change in the full-back positions. Glen Johnson making a substitute appearance in the role on Sunday could mean he'll be an option.
Last season Rodgers bemoaned the lack of squad depth but there are plenty of options available for the side going into this week's game, though it's doubtful he'd make too many changes. But some will prove to be essential.