Objective: The aim was to examine the impact of receipt of mental health services on health care expenditures for U.S. adults with major chronic physical conditions. Methods: Medical Expenditure Panel Survey data for 2004-2014 were analyzed for adults ages $18 with at least one of six chronic physical conditions (cardiovascular diseases, cancer, diabetes, emphysema, asthma, and arthritis) who were followed up for 2 years (N533, 419). Outcomes included overall health care spending and expenditure by service type (inpatient services, outpatient services, emergency department visits, office-based physician visits, and prescribed medication). A difference-in-differences model compared a change in health care costs in the subsequent year for those who did and did not receive mental health services in the preceding year. Results: On average, the increase in overall health care expenditure in the subsequent year among adults receiving mental health services in the preceding year was smaller by 12.6 percentage points (p, 0.05) than for those who did not receive such services. The difference was equivalent to $1, 146 in 2014 constant U.S. dollars (p50.05). Medication treatment alone did not have a meaningful effect on overall costs. The combination of psychotherapy and medication was associated with a per-capita reduction in overall health care expenditure of 21.7 percentage points, or $2, 690 (p, 0.01). The combination was also associated with reduced costs for office-based visits (p, 0.05) and medication (p, 0.05). Conclusions: Receipt of mental health services was associated with a reduction in overall health care costs, particularly for office-based visits and prescribed medication, among adults with chronic physical conditions.