Background: The global epidemic of unhealthy lifestyle causes to increase chronic disease. It has been proven that psychological factors such as self-efficacy are responsible to success in the process of lifestyle change. Low self-efficacy is usually related to low level of physical activity and medication adherence. Objective of the study was to investigate the effects of self-efficacy, other physical symptoms on physical activity and medication adherence in patients with chronic illness in public health centers. Materials and Methods: A cross-sectional study was conducted on 483 patients with chronic diseases attended to governmental health care centers in Isfahan. Participants were chosen by systematic random sampling. Inclusion criteria were having a chronic illness at least 6-month ago while prescription of medication and willing to take part in the survey. The parts of Stanford Self-management Questionnaire were used. Data were analyzed by SPSS 18 software using the descriptive and analytic statistics. P <0.05 was considered significant. Results: Mean age of participants was 54.8 (7.22) years. The half of participants had low self-efficacy and 87.2% had low physical activity. Nearly 80% of patients had a good medication adherence. There was a significant relationship between self-efficacy and physical activity (P = 0.336, β = 1.01, P< 0.001). Conclusion: Although chronic disease patients had a good medication adherence, other self-care behaviors such as physical activity has been neglected. It is seemed that concentration on psychological factors such as self-efficacy should be considered as a proximal factor to improve self-care.