The Boys in Green were beaten 3-2 by Serbia on Wednesday night despite taking an early lead. Aleksandar Mitrovic came off the bench in the second half to net a brace and condemn the visitors.
As disappointing as Stephen Kenny's side were, they'll be confident of getting their campaign up and running against a side languishing 98th in the FIFA rankings.
Die Roten Löwen were in action on Wednesday night against next year's hosts Qatar in an international friendly. The Europeans went down 1-0 in a dour loss.
They're the team with the unwanted distinction of participating in the most World Cup qualifiers without ever making it to the finals. They have been drawn in another daunting group that also features reigning European champions Portugal.
Republic of Ireland vs Luxembourg Head-To-Head
In five previous meetings, Ireland have held a perfect record by winning all five of their games against Luxembourg. The last time these teams met was in 1987.
Republic of Ireland Form Guide (all competitions): L-L-L-D-L
Luxembourg Form Guide (all competitions): W-L-L-D-L
Republic of Ireland vs Luxembourg Team News
Republic of Ireland
Stephen Kenny has been able to call upon several well-known players such as Seamus Coleman, Shane Duffy, Shane Long, James McClean, and Jeff Henrick.
West Ham's Conor Coventry is in line for his international debut.
There are quite a few injury concerns for the Irish. Kevin Long, Conor Hourihane, James McCarthy and Harry Arter are all injured, while Derrick Williams is down with COVID-19.
Injured: Kevin Long, Conor Hourihane, James McCarthy, and Harry Arter
Unavailable: Derrick Williams
Veteran players such as Lars Krogh Gerson, Laurent Jans, Chris Phillips, Stefano Bensi and Maurice Deville have been recalled. Meanwhile, Lucas Fox is the only player in line to make his debut.
Dirk Carlson is a notable absentee for Luxembourg as he's currently injured.
Injured: Dirk Carlson
Republic of Ireland vs Luxembourg Predicted XI
Republic of Ireland (3-5-2): Mark Travers; Seamus Coleman, Dara O'Shea, Ciaran Clark; Matt Doherty, Jayson Molumby, Josh Cullen, Alan Browne, Enda Stevens; Callum Robinson, Aaron Connolly.
Luxembourg (4-2-3-1): Anthony Moris; Laurent Jans, Maxime Chanot, Lars Krogh Gerson, Mica Pinto; Christopher Martins, Vincent Thill; Maurice Deville, Danel Sinani, Florian Bohnert; Edvin Muratovic.
Republic of Ireland vs Luxembourg Prediction
Ireland put up a good fight in their defeat against Serbia and a similar performance at the weekend should help them see off the visitors.
Prediction: Republic of Ireland 3-0 Luxembourg