Neither nation qualified for the forthcoming World Cup, meaning this friendly - which is being held at the Daren Sammy Cricket Ground - is more about building confidence for the future.
Match preview
Since attempting to qualify for the World Cup for the first time in the early 1990s, St Lucia have never come particularly close to reaching international football's grandest tournament.
Their best achievement was advancing beyond the first round of CONCACAF qualifying for the 2014 World Cup in Brazil, but they finished bottom of Group D with only one point from six matches.
More recently, St Lucia decided to withdraw from qualifying for the 2022 World Cup for unknown reasons, but they did play their first fixtures since the coronavirus pandemic in June earlier this year, beating Dominica and Anguilla to gain promotion to the second tier of CONCACAF's Nations League.
As such, they will have confidence of beating the lowest-ranked nation in world football on Thursday, with head coach Stern John hoping to build on his decent start in charge after being appointed in May.
Indeed, San Marino's 1-0 win over Liechtenstein in a friendly in April 2004 remains their only ever victory as a footballing nation since playing their first official match in 1990.
They have lost all but nine of the almost 200 matches they have played, drawing on eight occasions, most recently in a friendly against Seychelles in September.
Seemingly, the San Marino Football Federation is determined to break their winless cycle and move up the FIFA World Rankings as a result, as they are increasingly organising friendlies against weaker nations from other federations.
Having finished bottom of their Nations League group in the bottom tier for the third successive campaign, head coach Fabrizio Costantini needs all the help he can get get his hands on to turn his nation's fortunes around ahead of two back-to-back friendlies on the Caribbean island.
Saint Lucia form (all competitions):
W
W
San Marino International Friendlies form:
L
L
L
D
San Marino form (all competitions):
L
L
L
L
D
L
Team News
St Lucia's key figure in their squad is arguably Kurt Frederick, who has scored eight goals from 46 caps for his country despite often playing as a left-back.
Doneal Lionel will be hoping to make his international debut against San Marino.
The visitors, meanwhile, have much more international experience within their ranks, with Mirko Palazzi their most capped player with 70 and counting.
However, there are still seven potential debutants making the trip to St Lucia, with two fixtures in the space of four days likely to see most of them appear on the pitch at some point.
Saint Lucia possible starting lineup:
Barclett; Myers, Doxilly, Thomas, Evans; Frederick, Pearson; Davies, Roserie; McFarlane, Remy
San Marino possible starting lineup:
Benedettini; Franciosi, Palazzi, Tosi; Zafferani, Mularoni, Golinucci, Rinaldi, Grandoni; Rinaldi, Vitaioli
We say: Saint Lucia 0-0 San Marino
San Marino are often well organised defensively but find goals extremely hard to come by, so we can envisage them avoiding defeat for only the 10th time in their history.
St Lucia may be rusty having only played two fixtures in the last three years, so they could settle for a draw ahead of targeting a win against the same opponents on Sunday.