BACKGROUND: Ramadan fasting involves refraining from food and liquids from the sunrise till sunset for one month yearly; affecting the sleep pattern and duration, physical activity, and meal number and composition leading to biochemical and physiological changes in the body. Irisin, adiponectin, and leptin induce multiple metabolic effects. OBJECTIVE: The aim of this study is to examine the effect of the Ramadan fasting on serum levels of irisin, adiponectin, and leptin. MATERIALS AND METHODS: A total of sixty healthy students (43 females and 17 males) were recruited, 20.9 years mean age, who were fasting for Ramadan were included in this study. Anthropometry, blood samples and physical activity were determined. Lipid profiles were determined using an enzymatic colorimetric method, and serum levels of irisin, adiponectin, and leptin were measured using Enzyme-linked Immunosorbent Assay. All measurements were measured before Ramadan and in the fourth week of Ramadan. RESULTS: Subjects experienced a significant increase in LDL was determined during Ramadan vs before Ramadan (142.8 vs. 158.1 mg/dl p = 0.03) along with a significant reduction in leptin, adiponectin and irisin concentration during Ramadan compared to before Ramadan (11.6 vs. 8.6; p = 0.000; 4.42 vs. 3.58; p = 0.022; 33.6 vs. 16.3; p = 0.003). A significant positive correlation was found between physical activity and irisin concentration before Ramadan (r = 0.338, p = 0.022). CONCLUSIONS: Ramadan fasting has significant effects on irisin, adiponectin, and leptin levels. Their levels were significantly reduced during Ramadan while LDL level was increased. Irisin level has a significant correlation with the physical activity of the participants.