The teams meet at Narodny Atleticky Stadion, in Banska Bystrica, with the Young Lions' opponents also seeking three points following an opening draw with Israel.
Match preview
Seeing off a competitive Austria team, who had eliminated Spain in qualifying, England started their quest for the Euro 2022 trophy with a merited win at the weekend.
A pair of well-crafted goals secured their 2-0 victory on the opening day of an intense group-stage schedule, which features three matches within less than a week: Aston Villa's Carney Chukwuemeka netted the first, before laying on the second for Alfie Devine in the 65th minute.
One of the tournament favourites, Ian Foster's team managed to prolong the momentum that previously helped them cruise through qualifying, and they already have one eye on reaching the final in Trnava, on July 1.
In the elite round, earlier this year, the Young Lions recorded consecutive wins over the Republic of Ireland, Armenia and Portugal - scoring nine times and conceding just once - and they have now gone unbeaten through their last seven matches.
Last winners in 2017, England will take to the field with three points already in the bag, and another victory should send them through: the top two teams in both groups progress to the semi-finals, and all four will automatically qualify for the 2023 Under-20 World Cup in Indonesia.
The winner of a playoff between the sides finishing third can also book their flights for next year's global finals, so Serbia will be scrapping for every possible point too, after failing to beat Group B outsiders Israel on Sunday.
Indeed, the Israelis seemed set to win the teams' opening fixture, but a stoppage-time header from Stefan Lekovic salvaged a 2-2 draw for Aleksandar Jovic's side in Ziar nad Hronom.
Having gone ahead through Milan striker Marko Lazetic, the Orlici will rue their inability to defend such a lead, but after beating the Netherlands to qualification, they still represent a significant threat at this tournament.
Boasting a proud record at youth level, including being crowned European Under-19 champions in 2013, this latest Serbia squad remain undefeated in their last five matches and are not afraid to take the initiative.
England Under-19s European Under-19s Championship form:
England Under-19s form (all competitions):
Serbia Under-19s European Under-19s Championship form:
Serbia Under-19s form (all competitions):
Team News
With qualification still in the balance, and unfancied Israel yet to come, England are unlikely to make too many changes on Wednesday night, so coach Ian Foster should name a familiar side.
Top scorer during qualifying, with a tally of six goals, Tottenham Hotspur's Dane Scarlett should lead the line up front, with Aston Villa trio Jacob Ramsey, Tim Iroegbunam and Carney Chukwuemeka continuing to feature in midfield.
Brentford's Matthew Cox starts in goal, while Harvey Vale of Chelsea captains the side from the left flank.
Serbia, meanwhile, will start with Milan's Marko Lazetic up front in a probable 4-3-3 formation, with support from left-winger Nemanja Motika.
Fellow forward Ognjen Ajdar was the Orlici's leading scorer in qualification, and will hope for a starting place after appearing from the bench on Sunday.
Dorde Gordic is the youngest player in the Serbian squad, aged just 17, and is set to join captain Nikola Petkovic in a midfield trio.
England Under-19s possible starting lineup:
Cox; Norton-Cuffy, Quansah, Edwards, Doyle; Iroegbunam, Chukwuemeka; Devine, Ramsey, Vale; Scarlett
Serbia Under-19s possible starting lineup:
Lukic; Lazic, Lekovic, Ilic, Krsmanovic; Gordic, Petkovic, Knezevic; Miladinovic, Lazetic, Motika
We say: England Under-19s 2-1 Serbia Under-19s
After an impressive first outing, England's qualification for the knockout stage should be secured by a slim victory over Serbia, who have already proved they can be caught out defensively.