This prospective, field-based study examined the association between actigraphically measured total sleep time and incident illness including cold, flu, gastroenteritis and other common infectious diseases (e.g. strep throat) in adolescents during the course of a school semester. Participants were 56 adolescents ages 14-19 years (mean = 16.6, standard deviation = 1.2, 39% male) from five high schools in Rhode Island. Beginning in late January, adolescents wore actigraphs [mean 91 (19) days, range 16-112 days] and were assigned post-hoc to longer or shorter sleep groups based on median splits. Adolescents were interviewed weekly across as many as 16 weeks (modal number of interviews = 13) using a structured protocol that included 14 health event questions. Illness events and illness-related school absences were coded for 710 completed interviews, with 681 illness events and 90 school absences reported. Outcomes (illness bouts, illness duration and absences) were compared among sex, sleep and academic year groups using non-parametric regression. In a subset of 18 subjects, mean actigraphically estimated total sleep time six nights before matched illness/wellness events was compared using multivariate analysis of variance (MANOVA). Longer sleepers and males reported fewer illness bouts; total sleep time effects were more apparent in males than females. A trend was found for shorter total sleep time before ill events. The present findings in this small naturalistic sample indicate that acute illnesses were more frequent in otherwise healthy adolescents with shorter sleep, and illness events were associated with less sleep during the previous week than comparable matched periods without illness.