The present study investigated whether adjustment of coping strategies would predict the six-week course of fatigue symptoms in a primary care sample (N = 221) and whether the contribution of adjusting coping strategies would depend on the duration of fatigue at the time. It was hypothesized that the motivation to adjust coping strategies would be most present in people who are confronted with the possibility of their symptoms turning into a chronic condition, and not in people who have been fatigued for either a short period or a very long period. Moreover, it was hypothesized that adjustments in the employment of coping strategies are a better predictor of fatigue course than the continued use of particular coping strategies. Using a prospective design with a six-week follow-up, the results of a multisample LISREL analysis over four groups of participants differing in fatigue duration showed that adjustment of coping strategies is a significant predictor of the course of fatigue symptoms, and that a differential effect related to fatigue duration is present. Findings are discussed in the context of the role of coping in regulating psychosomatic symptoms.