In recent times the competition's players had voiced their interest in the return of the state format, with the main issue being when to fit it into the calendar.
But the concept is dead and buried, according to the AFL chief executive, who was in Sydney attending a function hosted by the GWS Giants.
"I don't think so," Demetriou said when asked if State of Origin would return.
"Mainly because I'm more of a pragmatist. As a viewer of sport at the national level, we've got the Australian cricket team, the Socceroos, the Wallabies, they're strong national teams.
"At state level, you can't get a better contest than (rugby league) State of Origin. It's an incredible event and the envy of all.
"The way the two states engage, the ratings, it's all fantastic.
"Our game has great club-versus-club football. That's our strength.
"Sometimes it's OK to acknowledge these are our strengths and these are our weaknesses."
Demetriou was asked about a range of issues, stating the Giants should be playing finals in quick time and would ultimately become a huge club.
He also suggested a potential Grand Final between GWS and the Sydney Swans down the track would be the highest rating match in AFL history.
The Swans' Grand Finals against Hawthorn last season and West Coast in 2006 are the two highest rating deciders to date.
The AFL boss was also quizzed about A-League side the Western Sydney Wanderers, who have been a revelation in the city's west and will play off in the grand final against Central Coast this Sunday.
While the Giants are still plugging away at establishing a base in the region, recently taking their membership past a healthy 12,500, the Wanderers have been a stunning success, playing to full houses all season.
Rather than see them as an impediment to the Giants, Demetriou believes the Wanderers' success is good for AFL's expansion in the area.
"I think the way they've performed has been remarkable and should be applauded," he said.
"The passion of their supporters is fantastic.
"Full credit to them. I wish them well and hope they win this week.
"I see that as a benefit to the Giants. Competition is a good thing and motivates people to be better and come up with new ideas."
James Dampney is a reporter for AFL.com.au. Follow him on Twitter: @AFL_JD
