Background: Evidence lacks on whether obesity along with major depression (MD)/anxiety leads to higher health care use (HCU) and health care-related costs (HCC) compared with either condition alone. The objective of the study was to examine the longitudinal associations of obesity, MD/anxiety, and their combination with HCU and HCC. Methods: Longitudinal data (2004-2013) among N = 2706 persons at baseline and 2-,4-, and 6-year follow-up were collected on obesity, MD/anxiety and HCU. Results: The combination of obesity and MD/anxiety was associated with an increased risk of primary and specialty care visits, and of hospitalizations, odds ratios (95%-confidence intervals): 1.83 (1.44; 2.34), 1.31 (1.06; 1.61) and 1.79 (1.40; 2.29) compared to non-obese and non-depressed individuals. The primary and specialty care costs were higher in persons with obesity and MD/anxiety than in persons without these conditions, but the relative excess risk due to interactions between obesity and MD/anxiety regarding HCU and HCC were not statistically significant (i.e. no synergistic effect). Conclusions: Obesity along with MD/anxiety leads to higher HCU and HCC over time. However, the HCC associated with the joint presence of both conditions are not higher than the sum of the HCC due to each condition independently.