Background Obesity is associated with low-grade systemic inflammation, and it has been suggested that increased inflammation markers could predict future weight gain. Our aim was to investigate the associations of high-sensitivity C-reactive protein (hs-CRP) concentration with changes in weight and waist circumference in adults during 11 years of follow-up. Methods We used data from the Health 2000 and Health 2011 surveys consisting of a population-based sample of Finnish adults. We included those 3143 participants, aged 30–75 years at baseline, whose baseline hs-CRP was measured, and who had information on measured weight and height at both time points. Associations between baseline hs-CRP and changes in weight and waist circumference were analyzed using multinomial logistic regression, adjusted for sociodemographic factors (age, sex, marital status, and educational status), lifestyle factors (smoking, alcohol consumption, leisure-time physical activity, sitting time, sleeping time, and psychological distress), and baseline values of BMI and waist circumference. Results Hs-CRP was not associated with weight gain (≥5%) when adjusted for potential confounders (OR 0.99, 95% CI 0.96–1.01), compared to stable weight (change <±5%). Higher baseline hs-CRP was associated with decrease in weight (≤−5%) in the unadjusted (OR 1.03, 1.01–1.05), but not in the adjusted (OR 1.01, 0.99–1.03) model. No association was observed between hs-CRP and waist circumference. Conclusions Hs-CRP was not associated with future changes in weight or waist circumference in adults. These findings suggest that hs-CRP concentration does not predict future weight gain.