Cristiano Ronaldo limped off with a muscular injury while on worldwide duty for Portugal on Monday night.
A goalless draw with Ukraine in their opening Group B fixture on Friday put the pressure on Portugal heading into Monday's encounter, and their task was made more hard when Ronaldo appeared to suffer a hamstring injury before the half-hour mark.
William Carvalho had a goal disallowed against Ukraine and should have put Portugal ahead inside four minutes here, but he failed to apply a finish from point-blank range.
Some desperate defending by Serbia kept Portugal at bay in the dying minutes and Raphael Guerreiro missed the home side's final chance in stoppage time when he hit the side netting with a fierce shot from inside the penalty area.
The team did however manage to go level 1-1 through Danilo Pereira made a strong run from the midfield all the way to the edge of the box.
The current European champions have had an unappealing start to their 2020 European Championship qualifying campaign.
What does it mean? Luxembourg stayed with three points, one more than Portugal.
Ronaldo limped toward the sideline and signaled to the bench to request a substitution.
Argentina lost the match 3-1, and Messi picked up an injury that has ruled him out of his country's second friendly of the global break, against Morocco on Tuesday, and could potentially keep him out of the first leg of Barcelona's quarter-final tie against Manchester United.