An outbreak of Chikungunya virus (CHIKV) illness associated with high fever combined with prolonged and severe arthralgias occurred on Grande Comore Island from January through May 2005; 5,202 cases were reported. A seroprevalence study was conducted to define the extent of transmission on the island. We conducted a cross-sectional survey using a multistage sampling technique. A total of 481 households were sampled. In each household, one resident was selected randomly for interview and blood collection. We administered questionnaires and tested 331 sera for CHIKV-specific IgM and IgG antibodies by capture enzyme-linked immunosorbent assay. Infection with CHIKV infection (seropositivity) was defined as presence of IgG and/or IgM antibodies to CHIKV. A total of 331 (69%) of 481 survey participants consented to blood collection. Antibodies to CHIKV were detected in 63% of sera; IgM antibodies were found in 60% of specimens and IgG antibodies were detected in 27% of specimens. Extrapolation of the findings to the entire Grande Comore population suggested that nearly 215,000 people were infected with CHIKV during the outbreak. A total of 79% of the seropositive persons were hospitalized or stayed at home in bed for a mean of 6 days (range = 1-30 days); 52% missed work or school for a mean of 7 days (range = 1-40 days). The findings suggest that CHIKV was broadly transmitted during the outbreak with a high attack rate. Although not fatal during this outbreak, CHIKV infection caused significant morbidity and decreased economic productivity.