Objectives. Due to increasing pressure on healthcare resources, knowledge of factors that affect healthcare utilization (HCU) is important. However, the evidence of a longitudinal association between loneliness and social isolation respectively, and HCU is limited. The present prospective cohort study investigated the association of loneliness and social isolation with HCU in the general population over time. Method. Data from the 2013 Danish “How are you?” survey (n = 27.501) were combined with individual-level register data with almost complete follow-up over a 6-year follow-up period (2013–2018). Negative binomial regression analyses were performed while adjusting for baseline demographics and preexisting chronic disease. Results. Loneliness measured was significantly associated with more general practice contacts (incident rate ratio [IRR] = 1.03, 95% confidence interval [CI] [1.02, 1.04]), more emergency treatments (IRR = 1.06, [1.03, 1.10]), more emergency admissions (IRR = 1.06, [1.03, 1.10]), and hospital admission days (IRR = 1.05, [1.00, 1.11]) across the 6-year follow-up period. No significant associations were found between social isolation and HCU with one minor exception, in which social isolation was associated with fewer planned outpatient treatments (IRR = 0.97, [0.94, 0.99]). Wald test demonstrated that the association of loneliness with emergency admissions and hospital admissions days was not significantly different from the effects of social isolation on those outcomes. Conclusions. Our findings suggest that loneliness slightly increased the number of general practice contacts and emergency room treatments. Overall, the effects of loneliness and social isolation on HCU were small.