During the 10-year period from 1997 through 2006, the reported mean annual incidence rate of leptospirosis in the state of Hawaii was 3.3/100,000 with a range of 22-60 infections reported each year. Because the clinical presentation is highly variable, however, leptospirosis illness is challenging to recognize and may be underdiagnosed. To assess whether the incidence may be substantially higher than reported figures indicate, we retrospectively studied the prevalence of anti-Leptospira IgM antibodies among specimens obtained over a 12-month period (May 2001 to April 2002) from patients presenting with febrile illness during a dengue fever outbreak in Hawaii. Of 1206 patients testing negative or indeterminate for dengue, 54 (4.5%; 95% confidence interval: 3.3%-5.7%) were positive for anti-Leptospira IgM antibodies using a commercially available dipstick enzyme-linked immunosorbent assay (ELISA). The most common clinical symptoms reported by laboratory-positive leptospirosis patients were fever (92%), headache (88%), and myalgia (83%). Three clinical symptoms were significantly less common among persons laboratory positive for leptospirosis when compared with the 122 patients who had been diagnosed with dengue fever during the outbreak: rash (p < 0.0001), chills (p = 0.05), and petechiae (p = 0.0005). Laboratory-positive leptospirosis infections were identified in persons exposed on each of the 5 most populous islands and illness onsets spanned a 10-month period, reflecting an endemic pattern of disease. If added to the figures obtained via routine passive surveillance, the number of leptospirosis infections identified through this study would more than double the annual incidence rate for Hawaii during 2001. These findings indicate that many leptospiral infections in Hawaii go undiagnosed. Physicians should maintain a high index of suspicion for leptospirosis when assessing patients presenting with acute febrile illness among residents and visitors to Hawaii.