Among 1,349 Streptococcus pneumoniae invasive isolates, 45 (3.3%) were levofloxacin resistant. Serotype distribution was as follows: 8 (n=32 isolates), 19A (n=4 isolates), 7F (n=3 isolates), 9V (n=2 isolates), 10A (n=1 isolate), 19F (n=1 isolate), 6B (n=1 isolate), and nontypeable (n=1 isolate). Levofloxacin-resistant isolates had dual mutations in the gyrA and parC genes. Serotype 8 strains corresponded to a capsular switching of the Sweden(15A)-25 clone. Levofloxacin resistance was also detected among multiresistant (ST276(19A), Spain9V-ST156, ST88(19F), and ST1542(6B)) and among usually antibiotic-susceptible (Netherlands7F-ST191, ST1201(19A), and ST2639(10A)) clones.