Excluding qualifiers, this will be the first European meeting between a Russian and Swedish team since October 2007, when Spartak Moscow eliminated BK Hacken in the first round of the UEFA Cup.
Zenit St Petersburg extended their unbeaten domestic run to 18 matches when they came from behind to beat Krylya Sovetov 2-1 in the Russian Premier League last weekend.
After Anton Zinkovsky had opened the scoring for the visitors in the 14th minute, experienced striker Artem Dzyuba headed in an equaliser midway through the first half, before the comeback was completed in the 79th minute when Aleksei Sutormin converted from the penalty spot.
Sergei Semak's side sit four points clear at the top of the table and are one of only two Russian top-flight sides who remain unbeaten after nine league games.
Domestic dominance has been achieved by Zenit and they seek a fourth successive Premier League title, though the club now hopes to progress in Europe and reach the knockout stages of the Champions League for the first time since 2015-16.
If they are to claim a top-two spot in Group H or even third place - which would see them drop down into the Europe League - then victories in both encounters against Malmo will likely be imperative. However, Zenit head into Wednesday's game after losing four of their last seven home games in Europe.
While Zenit are in the early stages of their title defence, Swedish champions Malmo have just nine league games remaining to try and climb to the top of the Allsvenskan table.
An impressive 5-1 home victory against relegation-threatened Orebro means the Sky Blues remain in second and just three points behind league leaders Djurgarden.
Jon Dahl Tomasson's men - who secured their 21st Swedish title last season and their fifth in the last eight years - are determined to finish at the summit this year, though a prolonged spell in Europe is also high on the agenda.
Malmo, who are considered as the outsiders in Group H, have lost their last four Champions League matches by an aggregate score of 20-0, the most goals conceded by any side in the competition's history over a period of four fixtures.
Success on Wednesday is not expected for the Sky Blues, though Tomasson will be keen to see his side put up a fight against a Zenit outfit, who are realistically the most likely opponent they are to claim three points against.
Zenit St Petersburg Champions League form:
Zenit St Petersburg form (all competitions):
Malmo Champions League form:
Malmo form (all competitions):
Zenit will be without former Liverpool centre-back Dejan Lovren, who is suffering with a leg injury, while Magomed Ozdoyev and Vyacheslav Karavayev are also on the treatment table.
Defensive midfielder Wilmar Barrios has featured as a centre-back in each of the last three matches, including the defeat against Chelsea, and the Colombian is set to start in the back three once again alongside Dmitriy Chistyakov and Yaroslav Rakitskiy.
Iranian forward Sardar Azmoun, who scored 17 league goals last season and has six strikes to his name this campaign, is expected to lead the line alongside Dzyuba, who is one goal away from becoming the first Russian player in Champions League history to reach double figures.
As for Malmo, 35-year-old forward Ola Toivonen as well as Jonas Knudsen, Oscar Lewicki and Niklas Moisander are all ruled out with knee injuries.
Former Blackburn Rovers and Norwich City defender Martin Olsson could be handed a start at left wing-back ahead of Soren Rieks, with either Eric Larsson or Jo Inge Berget set to start on the opposite flank.
Central midfielders Anders Christiansen, Bonke Innocent and Erdal Rakip are all likely to remain in the starting lineup, while striker Antonio Colak, who has scored 10 goals so far this season, is expected to play alongside Veljko Birmancevic up front.
Zenit St Petersburg possible starting lineup:
Kritsyuk; Barrios, Christyakov, Rakitskiy; Sutormin, Kuzyayev, Wendel, Santos; Malcom, Dzyuba, Azmoun
Malmo possible starting lineup:
Diawara; Larsson, Ahmedhodzic, Brorsson, Nielsen, Olsson; Rakip, Innocent, Christiansen; Birmancevic, Colak
We say: Zenit St Petersburg 2-0 Malmo
Both Zenit and Malmo will view this fixture as a must-win game if they are to have any chance of progressing to the knockout stages.
The hosts are the strong favourites to come out on top at the Krestovsky Stadium, and we feel they should have few problems in securing a routine victory on Wednesday.