Researchers conducted a cross-sectional retrospective study. For an investigation, the researchers sought to assess the additional healthcare costs of depression in patients with spine disease and learn more about the factors contributing to the elevated cost burden. From 2007 to 2015, data was gathered from the Medical Expenditure Panel Survey. Concurrent depression International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes was used to identify and stratify spine patients. A multivariate 2-part logistic regression with adjustments for sociodemographic factors and the Charlson Comorbidity Index was used to compare health care consumption and expenditures between individuals with and without depression. The study comprised 37,094 participants over the age of 18 who had a spine problem (mean expenditure: $7829±241.67). About 7,986 patients were depressed (mean expenditure: $11,455.41±651.25), while 29,108 were not depressed (mean expenditure: $6837.89±244.51). The cost of care for spine patients with depression was 1.42 times greater than for patients without depression (95% CI: 1.34–1.52; P<0.001). The incremental cost of treating depression in spine patients was $3388.22 (95% CI: 2906.60–3918.96; P<0.001). Compared to the non-depressed sample, comorbid depression was related to higher inpatient, outpatient, emergency department, home health, and prescription medication utilization and costs. Patients with depression in the spine had an about $3500 higher annual incremental economic cost than those without depression. When extrapolated nationally, this leads to an additional $27.5 billion in yearly added expenditures that can be directly ascribed to depression among spine patients, or nearly 10% of the total anticipated national spending on depression. Strategies aimed at improving depression treatment have the potential to reduce healthcare expenses for spine surgery patients significantly.