Background Although the serum adiponectin level is inversely correlated to body mass index and closely associated with obesity and related diseases, neither the impact of weight loss on the adiponectin level nor other factors that might influence the adiponectin level during weight loss intervention are well documented. Objective The objective of the study is to assess the change in the serum adiponectin level during weight loss intervention and to determine if sleep parameters affect the serum adiponectin level. Methods Ninety women with overweight or obesity aged 25 to 65 years completed a 7-month cognitive behavioural therapy based weight loss intervention that included dieting, exercise and stress management. Serum adiponectin level, body fat percent, symptoms of depression and anxiety and objective sleep parameters, assessed by actigraphy, were measured at baseline and at the end of the intervention. Results The serum adiponectin level was significantly increased after the weight loss intervention (P < 0.001). In a multiple regression analysis, the change of the adiponectin level was positively associated with the magnitude of body fat loss (beta = -0.317, P < 0.001) and an increase of sleep minutes (beta = 0.210, P = 0.043). Conclusion An increase in objective sleep duration was related to a significantly increased serum adiponectin level independently of the change of body fat during the weight loss intervention.