Previous research has found that chronic fatigue syndrome (CFS) patients report increased susceptibility to upper respiratory tract illnesses (URTIs) when compared with healthy volunteers. This study aimed to replicate and extend this research by investigating the role of psychological distress (stress and negative mood) in the recurrence of URTIs in CFS patients as well as its role in the recurrence of CFS symptoms. A 15-week diary study. Measures of psychological stress, negative mood, recurrence of URTIs and symptoms were recorded each week for a 15-week period. CFS patients (N=21), who had been assessed and diagnosed according to the Oxford criteria, were recruited from the Cardiff Chronic Fatigue Clinic and compared with a matched group of healthy controls (N=18). Frequency of occurrence of infectious illness and the relationship between psychological stress/negative mood and occurrence of illness were assessed. CFS patients reported more URTIs than the controls. Stress scores (and negative mood) were significantly higher in the week prior to the occurrence of URTIs than in weeks when no subsequent illness occurred. High levels of psychological stress also preceded the severity of reported symptoms of fatigue in the CFS group. CFS patients reported more frequent URTIs than healthy controls and these recurrences were preceded by high levels of psychological stress. High levels of stress were also associated with greater subsequent fatigue. Possible explanations of these results are discussed.