O'Neill has added the Rangers midfielder to a squad depleted by suspensions after Chris Brunt and Kyle Lafferty were sent off in Friday's defeat to Portugal.
There are also fitness concerns over Jamie Ward and Shane Ferguson, who both limped off in the second half of the Windsor Park clash.
Ward's 52nd-minute strike had given Northern Ireland a shock 2-1 lead after visiting striker Helder Postiga had been sent off for a head-butt.
But Brunt's dismissal preceded a two-goal blast from Cristiano Ronaldo, and the Real Madrid star completed a 15-minute hat-trick shortly after Lafferty became the third dismissal of the game.
Brunt and Lafferty are both suspended for the trip to Luxembourg, while an Irish Football Association official revealed that Niall McGinn was also nursing an injury.
Martin Paterson and Gareth McAuley both sat out training on Monday evening as a precaution but are expected to feature.
Luxembourg, currently bottom of Group F, held Northern Ireland to a 1-1 draw at Windsor Park in the opening game of the campaign a year ago.
Shiels has not featured for his country since the home draw against Azerbaijan in November last year.
Luxembourg v Northern Ireland is live on Sky Sports 2HD at 7pm