Physical inactivity has been postulated as mediator of the relationship between cancer-related symptoms and psychoneurobiological alterations. The aim of the study was to evaluate the influence of physical inactivity level on mood state, fitness level as well as on salivary markers of the hypothalamic-pituitary-adrenal axis (cortisol) and the SNS (-amylase) in breast cancer survivors. One hundred and eight breast cancer survivors (stages I-IIIa) participated in this cross-sectional study. Data were gathered on the following: Minnesota Leisure Time Physical Activity Questionnaire, profile of mood state, 6-min walk test, force handgrip, blood pressure, salivary cortisol concentration and salivary -amylase activity. For our analysis, two groups were formed based on physical activity level measured as energy expenditure during diary leisure activities of the participants at the moment of the study, a physical inactivity level group (<3 METs x h/week) and an adequate physical activity level group (>3 METs x h/week). Fitness level was significantly higher in the active than the inactive group, while anger, fatigue, depression, confusion, mood disturbance, diastolic blood pressure and salivary -amylase activity were significantly greater in the inactive than the active group. These results suggest that physical inactivity induces a worse psychoneurobiological state in inactive than in active breast cancer survivors.