Seventeen Klebsiella pneumoniae isolates producing the OXA-48 carbapenemase, obtained from 10 patients hospitalized from April to June 2010, mostly in the medical intensive care unit of the Villeneuve-Saint-Georges Hospital in a suburb of Paris, France, were analyzed. Seven patients were infected, of whom five were treated at least with a carbapenem, and five patients died. Molecular analysis showed that the isolates belonged to a single clone that harbored a 70-kb plasmid carrying the blaOXA-48 gene and coproduced CTX-M-15 and TEM-1 β-lactamases. This is the first reported outbreak of OXA-48-producing K. pneumoniae isolates in France.