The two countries find themselves in group two of League D alongside Malta and will be vying to get off to a winning start.
Match preview
Estonia head into their second round of games of 2022 on the back of a tough World Cup Qualifying campaign last year, in which they managed to earn just four points.
They were, at least, able to beat Belarus 2-0 on home turf in October but went on to finish with consecutive defeats at the hands of Wales, Belgium and Czech Republic, leaving them fourth in the group and a long way short of reaching their first ever major tournament.
Thomas Haberli's squad will now aim to improve their fortunes in the Nations League after dropping out of League C recently, as they placed at the bottom of their group with just three points from six games.
The Sinisargid then had to take on Cyprus in a two-legged relegation playoff in March, and, after a goalless stalemate in Tallinn, they made the trip and fell to a 2-0 defeat as Marinos Tzionis and Pieros Sotiriou found the net.
That has seen Estonia drop into the bottom division of the Nations League for the upcoming campaign, and they will be keen to kickstart their bid for a promotion with an opening win at home.
San Marino, meanwhile, will make the trip hoping for just a second victory in their international history.
You now have to go back over 18 years to find the European minnows' only triumph against Liechtenstein, while they have never managed to pick up a victory in a competitive fixture.
Their last UEFA Nations League campaign came to an end in 2020 with consecutive draws against Liechtenstein and Gibraltar after suffering defeats in the previous meetings with the two, seeing San Marino finish at the foot of Group D2 as a result.
Now under the management of Fabrizio Constantini, the European minnows were most recently in action in March, losing 2-1 and 2-0 in friendlies against Lithuania and Cape Verde respectively after a World Cup Qualifying campaign in which they failed to pick up a single point in 10 attempts, conceding 45 goals in the process.
With the aim of lifting spirits with a positive result away from home, San Marino will look to spring a surprise when they travel to Tallinn on Thursday.
Estonia Nations League form:
Estonia form (all competitions):
San Marino Nations League form:
San Marino form (all competitions):
Team News
Rauno Sappinen is a notable absentee from the Estonia squad, with the 45-capped attacker missing the end of the Polish domestic campaign due to injury.
In his absence, attacking responsibility could fall on Henri Anier and Sergei Zenjov, with the duo boasting 17 and 14 international goals respectively.
Midfielder Konstantin Vassiljev will continue to don the captain's armband, having turned out 139 times and scored 25 goals for his country.
San Marino have been unable to call on important attacker Filippo Berardi, who is sidelined by a knee injury.
Striker Matteo Vitaioli boasts the most experience in the squad with 74 international caps to his name, albeit having scored just one goal, while Adolfo Hirsch should also keep his place in the front line.
Defenders Dante Rossi, Filippo Fabbri and Andrea Grandoni are also out of the squad, with 35-year-old Mirko Palazzi expected to command a changed back line in their absence.
Estonia possible starting lineup:
Igonen; Paskotsi, Mets, Tamm, Kuusk, Pikk; Vassiljev, Kreida, Kait; Anier, Zenjov
San Marino possible starting lineup:
Benedettini; Battistini, Palazzi, Cevoli; Tomassini, E Golinucci, A Golinucci, Mularoni, Conti; Vitaioli, Hirsch