We conducted a seroepidemiologic study during an outbreak of pandemic (H1N1) 2009 in a boarding school in England. Overall, 353 (17%) of students and staff completed a questionnaire and provided a serum sample. The attack rate was 40.5% and 34.1% for self-reported acute respiratory infection (ARI). Staff were less likely to be seropositive than students 13-15 years of age (staff 20-49 years, adjusted odds ratio [AOR] 0.30; >50 years AOR 0.20). Teachers were more likely to be seropositive than other staff (AOR 7.47, 95% confidence interval [CI] 2.31-24.2). Of seropositive persons, 44.6% (95% CI 36.2%-53.3%) did not report ARI. Conversely, of 141 with ARI and 63 with influenza-like illness, 45.8% (95% CI 37.0%-54.0%) and 30.2% (95% CI 19.2%-43.0%) had negative test results, respectively. A weak association was found between seropositivity and a prophylactic dose of antiviral agents (AOR 0.55, 95% CI 0.30-0.99); prophylactic antiviral agents lowered the odds of ARI by 50%.