Both teams are just two games away from sealing a place in the biggest club competition and they will be keen to get off to a good start.
Match preview
Maccabi Haifa suffered a 2-0 defeat against Apollon Limassol in the return leg of their Champions League qualifying third-round tie last Tuesday.
First-half goals from Hervin Ongenda and Israel Coll saw Barak Bakhar's men come away empty-handed from their trip to the GSP Stadium in Nicosia.
However, the loss would turn out to be inconsequential for Maccabi, who had earlier claimed a 4-0 first-leg over their opponents from Cyprus.
Next up for the The Greens is the penultimate step towards securing a return to Europe's premier club tournament for the first time since 2006.
Off the back of an emphatic display in their most recent home outing, Wednesday's hosts will be hopeful of a repeat here to put them in the driving seat.
Red Star Belgrade made it seven victories on the bounce to start the new season as they brushed aside FK Vozdovac in a 4-0 rout on Saturday.
Goals from Aleksandar Pesic, Osman Bukari, El Fardou Ben and Mirko Ivanic secured a more-than-deserved three points for Dejan Stankovic's men at the Stadion Rajko Mitic.
Just before that, The Red-Whites comfortably beat Armenian outfit Pyunik Yerevan 2-0 on August 9 to secure a commanding 7-0 victory on aggregate.
Having come out on top in all but one of their last eight matches away from home, Wednesday's visitors have proven themselves to be a real force to reckon with on the road and will be keen to serve up a reminder.
Maccabi Haifa Champions League form:
Maccabi Haifa form (all competitions):
Red Star Belgrade Champions League form:
Red Star Belgrade form (all competitions):
Team News
Milan Rodic was suspended for Red Star's last European outing but the defender is expected to come back into the starting XI for this one.
Ghana international Osman Bukari has scored five goals in his last four games for the visitors, making him one to keep an eye on here.
Ali Mohamed was at the double for Maccabi Haifa against Apollon earlier this month and the 26-year-old will be looking to deliver the goods once again.
Defender Pierre Cornud could return to the lineup here after having to make do with a second-half cameo in the hosts' most recent involvement.
Maccabi Haifa possible starting lineup:
Cohen; Sundgren, Planic, Goldberg, Cornud; Chery, Lavi, Mohamed; Haziza, Pierrot, David
Red Star Belgrade possible starting lineup:
Borjan; Erakovic, Milunovic, Dragovic, Rodic; Kangwa, Kanga, Bukari, Ivanic; Pesic, Katai