This study sought to investigate whether the effects of spa therapy are subject to seasonal variation as suggested by conventional spa therapy research. A total of 268 female (age 31-90 yr) and 119 male (age 35-85 yr) patients with noninflammatory chronic pain were studied. Patients stayed at an Austrian spa for 3 wk and received 2-4 treatments per day, including mudpacks, massages, and exercise therapy. In different groups of patients for 2 yr, pain (self-assessed by questionnaire and Likert scales) and associated variables (mood, fatigue) were measured at the beginning, end, and 6 wk after spa therapy. Data were analyzed by multivariate analysis of covariance controlling for possible group differences between seasons and cosinor analysis. The effect of spa therapy on pain was seasonally dependent; short-term decrease of pain was best between April and June and medium-term decrease of pain was best between October and November, with a second minor peak in fall and spring, respectively. The magnitude of the seasonal variation was greater for back (approximately 30%) than for joint (approximately 20%) pain. Positive mood also improved most between April and June. The observed semi-annual variations of pain do not correspond to the well-known annual change in many physiological and psychological variables. The results suggest that the effects of spa therapy and possibly other related treatments, such as physical and alternative therapies, are subject to seasonal variation.