Objective: To study the effect of seasons on the health-related quality of life (HRQL) of asthmatic children. Methods: Four groups of asthmatic children 7 to 14 years old were recruited by pediatricians during each season of the year. Their HRQL was assessed by means of the Paediatric Asthma Quality of Life Questionnaire (PAQLQ). Other factors surveyed were asthma severity, atopy, medical treatment, immunotherapy, obesity, parental smoking, and anti-allergic measures. Results: The mean (SD) overall PAQLQ score was highest in summer at 6.2 (1.0) and lowest in autumn at 5.5 (1.2). The same trend was found for domains in summer and autumn, respectively: symptoms, 6.2 (1.0) vs 5.4 (1.4); emotions, 6.5 (0.8) vs 6.0 (1.0); and activities, 5.9 (1.4) vs 5.0 (1.5). Factors such as male gender (odds ratio [OR], 0.60; 95% confi dence interval [CI], 0.41–0.87), being on immunotherapy (OR, 0.59; 95% CI, 0.38–0.92), living in an urban environment (OR, 0.56; 0.33–0.93), and residing on the northern coast of Spain along the Bay of Biscay (OR, 0.56; 0.36-0.89) were independent protective factors against having a total PAQLQ score in the lower tertile. Conversely, being recruited in a primary care setting (OR, 1.55; 1.01–2.38) and having more severe asthma were risks for being in the lower tertile. Conclusions: Irrespective of the severity of the disease, season has a significant influence on the HRQL of asthmatic children.