The centre-back is expected to start for Argentina in their World Cup qualifier against Bolivia on Wednesday (AEDT), with Ramiro Funes Mori and City team-mate Nicolas Otamendi banned.
Demichelis, whose City contract expires at the end of the season, has won 49 caps for Argentina, but feels their game in Cordoba could be his last appearance for his country.
"As a matter of humility and because I am realistic of the situation, I have to be aware that it may be my last game," the 35-year-old told World D. "And I want to experience the game that way.
"I have been going 35-and-a-half years and do not know how many more chances I will be able to provide. I am proud to remain at my age, that they feel I can contribute.
"I'm not physically ill, but I know that there are new players. The coach has to have an eye on the project.
"The truth is that for me the next World Cup is far for my body and my mind. All this makes me say that this may be my last game. And if it is my last will be the best place for me, which is Cordoba, where I played a few times."
Argentina beat Chile 2-1 on Friday to extend their unbeaten run to four matches, although they are fifth in the qualifying table, having lost to Ecuador in their first game.
Bolivia are second bottom after five games, having lost 3-2 to Colombia last week, with their only points coming in a 4-2 home win over Venezuela in November.
The visitors are without the suspended Edward Zenteno and Leonel Morales, while Damian Lizio has left the squad for the birth of his child.