We report data from a prospective observational study performed in Martinique during a co-epidemic of dengue virus serotype 2 (DENV-2) and serotype 4 (DENV-4). Among 70 serum samples from patients with DENV-2 (n= 21) or DENV-4 (n= 49) infections, 47 (67.1%) were positive for dengue nonstructural protein 1 (NS1). Antigenemia correlated with plasma virus load and was independent of immune status and the time of sampling. Increased viremia 4–6 days after onset of illness was associated with NS1 positivity, secondary infection, and severe disease. Testing for NS1 could help identify the potentially most severely ill patients during the critical phase of dengue.