PURPOSE To determine if irisin plasma levels are associated with regular physical activity, body composition and metabolic parameters in women subjected to calorie restriction. SUBJECTS AND METHODS We studied 42 women aged 34 ± 13 years with a body mass index of 27.7 ± 1.8 kg/m2, who were subjected to a calorie restriction for three months. At baseline and at the end of the study, weight, waist and hip circumference, laboratory parameters, body composition by DEXA, resting and activity energy expenditure by indirect calorimetry and 72 hours actigraphy were measured. Fasting serum irisin was quantified using an ELISA kit. RESULTS After the intervention period, participants lost 1.5 (0.4-3.4) kg and irisin levels did not change. Irisin baseline levels were positively but weakly correlated with the level of physical activity. This association was lost at the end of the intervention. No association was found between irisin levels and body composition or insulin sensitivity or their changes after calorie restriction. No association between serum irisin levels and PGC-1αexpression in peripheral blood mononuclear cells and serum irisin was observed. CONCLUSIONS Fasting serum irisin was weakly associated with usual physical activity and did not change after calorie restriction.