The Israeli champions are ultimately seeking a return to the group stage after tussling with several European giants last year, but their hosts also boast plenty of recent continental experience.
Match preview
Having required a second-leg comeback to see off Romania's SSC Farul last week, Sheriff Tiraspol were relieved to progress to the Champions League's second qualifying round for a fourth straight season.
Overturning a 1-0 deficit, the perennial champions of Moldova eventually went through 3-1 on aggregate, but it took extra time to see off their visitors - Jerome Ngom Mbekeli and Peter Ademo scoring the goals that prevented the tie going to penalties.
Sheriff have taken part in the Champions League qualifiers in each of the last 22 years, but the Transnistrian club have only once qualified for the prestigious group phase: in the 2021-22 campaign they became the first Moldovan team to do so, recording a shock 2-1 win over Real Madrid at the Santiago Bernabeu.
Eliminated in the playoff round last season, the Wasps later finished third in their Europa League group and then lost to Nice in the knockout phase of the Europa Conference League.
Roberto Bordin's side went on to secure the club's eighth consecutive Moldovan National Division title - posting seven wins in an unbeaten 10-game championship round - and they are now aiming for a return to Europe's top table.
While Wednesday's hosts required an extra half-hour to edge through to this stage of the process, Maccabi Haifa simply cruised past their first-round opponents, crushing Hamrun Spartans 6-1 on aggregate.
Completing the job at Sammy Ofer Stadium last week, the Israeli side scored twice in the second half to earn a 2-1 home win over the Maltese champions, who were competing in the Champions League for the very first time. Haifa's Haitian forward Frantzdy Pierrot stepped off the bench to seal the deal late on; taking his tally to three in two games.
Last year, the Greens made it all the way through to the autumn group phase, and in a quartet also featuring European heavyweights Paris Saint-Germain and Benfica, the embarrassment of being beaten 7-2 and 6-1 was partly compensated for by a famous defeat of Juventus.
Since they secured a third successive Israeli Premier League title last season, Messay Dego has taken over dugout duties from former boss Barak Bakhar, who opted for a switch to Serbian giants Red Star.
In addition to navigating the first round of Champions League qualifying, Dego has already steered his team to victory in the Israeli Super Cup this summer. Haifa lifted the trophy last Saturday, after beating Beitar Jerusalem 3-1; meaning they have scored nine times in their last three matches before this week's encounter with Sheriff.
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Maccabi Haifa Champions League form:
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Team News
Likely to line up in a 3-5-2 formation, with Henrique Luvannor and Jerome Ngom Mbekeli paired together up front, Sheriff should name a similar team to that which started last week's win over Farul.
Roberto Bordin has been busy in the transfer market this summer and he will have another option available on Wednesday. Joining a multinational squad in Tiraspol, Colombian defender Alejandro Artunduaga recently arrived from Once Caldas and could make an appearance on the left flank.
Meanwhile, Moroccan midfielder Amine Talal - formerly of Ligue 2 side Bastia - is set to captain the hosts from central midfield.
Maccabi Haifa will call upon veteran playmaker Lior Refaelov - who recently returned to the Greens from a long spell in Belgium - to create chances for their forwards on Wednesday.
Tjaronn Chery, scorer of the opening goal in Saturday's Super Cup win, is also a strong favourite to start in midfield, with Frantzdy Pierrot providing a distinct threat up front. Summer signings Anan Khalaili and Erik Shuranov are also contenders to feature in the visitors' forward line.
Sheriff Tiraspol possible starting lineup:
Koval; Garananga, Bueno, Zohouri; Tovar, Talal, Kyabou, Paulo, Artunduaga; Luvannor, Mbekeli
Maccabi Haifa possible starting lineup:
Nitzan; Sundgren, Seck, Goldberg; Sabia, Mohamed, Chery, Cornud; Refaelov; Pierrot, David