The 2006 Olympic champion crashed while attempting the triple Axel and failed to perform a quad. He was awarded 74.82 points - well short of his personal best score of 91.30 - to finish a disappointing sixth after Thursday's programme.
"I just can't skate the way I normally do and the reason is simple - it's a (back) injury which has been bothering me for a long time," Plushenko, who was seeking his eighth European men's crown in Zagreb, said.
The flamboyant Russian, widely regarded as the most gifted skater of his generation, was trailing leader Florent Amodio of France by 15 points, with Spain's Javier Fernandez a close second.
"Zhenya (Yevgeny) was in such pain he just couldn't go on," Plushenko's long-time mentor Alexei Mishin said.
"We can't take any risks with his health because we have a much bigger goal ahead of us - the (2014) Olympics in Sochi."
The men's title will be decided after the free skate on Saturday.
Plushenko, 30, missed almost a year through injury but made a triumphant comeback at last month's Russian championships in Sochi, easing to his 10th national title.
He underwent a knee surgery last February, a month after clinching his seventh European title in Sheffield, England.
Plushenko, who controversially lost the 2010 Olympic title to American Evan Lysacek, said he was hoping to be back on the ice later in the season.
"Now, I plan to travel to Germany to see a doctor. I'm not saying goodbye. I hope to see you soon," he said.