The hosts have only won two of their last 10 matches on home soil over the last two-and-a-half years, while the visitors have lost six of their last eight games on the road.
Match preview
Lithuania managed to avoid relegation from League C of the 2020-21 Nations League after securing a crucial 2-1 victory over Kazakhstan in their final fixture, which saw Arvydas Novikovas score a dramatic 94th-minute winner.
Since that victory, Rinktine have lost 12 of their last 15 matches across all competitions, including seven defeats out of eight 2022 World Cup qualifiers.
Lithuania (138th) now head into the new Nations League campaign as the lowest ranked nation in League C Group 1 behind the Faroe Islands (124th), Luxembourg (94th) and group favourites Turkey (43rd).
Valdas Ivanauskas's side can take some confidence from victories over Bulgaria and San Marino over the last eight months, but they head into Saturday's fixture having failed to win any of their last three meetings against Luxembourg.
Like Lithuania, Luxembourg were unable to qualify for the 2022 World Cup, but they did make a strong start to their campaign with two victories against the Republic of Ireland and Azerbaijan from their opening three matches.
The Red Lions secured another win over Azerbaijan later in the campaign and finished with nine points from eight fixtures, their highest-ever points total in World Cup Qualifying.
Luxembourg also had success in the 2020-21 Nations League, winning three and drawing one of their six fixtures, although they were unable to secure promotion from League C Group 1, as they finished three points behind group winners Montenegro.
Luc Holtz's side now turn their attention to the new Nations League campaign, and while finishing above Turkey could prove challenging, they should be confident of securing a second-place finish above the Faroe Islands and Saturday's opponents Lithuania.
After losing 1-0 to Lithuania in their first-ever encounter back in August 2009, Luxembourg have since beaten them twice, both by a 2-1 scoreline, and have played out a 1-1 draw at the LFF Stadium in their last meeting in June 2019.
Lithuania Nations League form:
Lithuania form (all competitions):
Luxembourg Nations League form:
Luxembourg form (all competitions):
Team News
Lithuania centre-back Egidijus Vaitkunas is ruled out through injury, so either Edvinas Girdvainis or Edgaras Utkus could be handed a start in the back three alongside Linas Klimavicius and Benas Satkus.
Thirty-eight-year-old Saulius Mikoliunas will be battling with Rolandas Baravykas for a place at right wing-back, while Augustinas Klimavicius, who scored on his international debut against San Marino in March, could keep his place in attack ahead of Karolis Laukzemis.
As for Luxembourg, Holtz is unlikely to make too many changes from the side which lost 1-0 to Bosnia & Herzegovina in their last international match three months ago.
The only potential change could see Lars Krogh Gerson replace Vahid Selimovic at centre-back, joining Florian Bohnert, Maxime Chanot and Mica Pinto in the back four.
Brothers Sebastien Thill, Olivier Thill and Vincent Thill will all be in contention to start in midfield, while Huddersfield Town's Danel Sinani is set to provide support in attack for lone striker Gerson Rodrigues.
Lithuania possible starting lineup:
Setkus; Baravykas, Satkus, Girdvainis, L. Klimavicius, Milasius; Lasickas, Slivka, Golubickas, Novikovas; A. Klimavicius
Luxembourg possible starting lineup:
Moris; Bohnert, Chanot, Gerson, Pinto; Martins, Barreiro; S. Thill; O. Thill, Sinani; Rodrigues
We say: Lithuania 1-2 Luxembourg
Both minnow nations have struggled to put together strong runs of form, but they will be hoping that their upcoming Nations League fixtures will provide them with an opportunity to turn their fortunes around.