BACKGROUND AND AIMS: There is a growing body of literature confirming the association between inflammation and obesity. Recent research suggests that inflammation may play a role in weight gain. The aim of the study was to analyse whether serum inflammatory markers predict weight gain or development of obesity in a prospective study design. METHODS AND RESULTS: The baseline study (DILGOM 2007) consists of a population-based sample of 5024 Finnish men and women aged 25-75 years, of whom 3735 participated in the follow-up study in 2014. Baseline data collection included a questionnaire on health behaviour, physical examinations and blood samples including serum high-sensitivity C-Reactive Protein (hs-CRP), Interleukin-1 receptor antagonist (IL-1Ra), Interleukin-6 (IL-6), Tumor Necrosis Factor Alpha (TNF-alpha) and high molecular weight adiponectin (HMW adiponectin). Indicators of obesity were weight, body mass index (BMI), waist circumference and body fat percentage (% body fat). At baseline hs-CRP, IL-1Ra, IL-6, TNF-alpha and HMW adiponectin associated strongly (p < 0.0001) with obesity indicators. After adjustment for several potential predictors of obesity, hs-CRP and IL-1Ra associated inversely with changes in obesity indicators during the 7-year follow-up. These associations disappeared, however, after further adjustment for baseline BMI. Only HMW adiponectin retained a modest positive association with the change in weight (p = 0.008), in BMI (p = 0.007) and in waist circumference (p = 0.002). CONCLUSION: These findings suggest that the inflammatory markers, although highly associated with obesity, do not predict weight gain in an adult population. This could translate into inflammation being a result of obesity rather than a contributing factor to it.