The impact of mental health comorbidities on outcomes after lumbar spine surgery in workers' compensation (WC) patients has not been robustly explored. The goal of this study was to examine the impact of mental health comorbidities on pain, disability, quality of life, and return to work after lumbar spine surgery in WC patients. A nationwide, prospective surgical outcomes registry (National Neurosurgery Quality Outcomes Database [N2QOD]) was queried for all patients who underwent 1- to 4-level lumbar decompression and/or fusion from 2012 to 2021. Patients were stratified on the basis of compensation status into non-WC (25,507) and WC (1018) cohorts. Baseline demographic data, perioperative safety data, and patient-reported outcome measures were compared between groups. The WC cohort was further subdivided on the basis of mental health status into patients with anxiety and depression (n = 107) and those without anxiety and depression (n = 911). Propensity matching was used to generate parity between these subgroups, generating 214 patients (107 pairs) for analysis. Perioperative safety, facility utilization, 1-year patient-reported outcomes (back and leg pain, disability, and quality of life), and return to work were measured as a function of WC and mental health comorbidity status. A total of 26,525 patients (25,507 non-WC and 1018 WC) who underwent 1- to 4-level lumbar spine surgery were reviewed. WC patients were younger, healthier (lower American Society of Anesthesiologists class), more likely to be minorities, less educated, and more likely to smoke and had greater baseline back pain, disability, and quality of life compared to non-WC patients. The prevalence of anxiety and depression was similar between groups (11%). WC patients had worse outcomes for all measures and lower rates of return to work compared to non-WC patients. WC patients with anxiety and depression demonstrated even greater disparities in all outcomes. After propensity matching, WC patients with anxiety and depression continued to demonstrate significantly worse outcomes in comparison to WC patients without anxiety and depression. Disparities in outcomes after lumbar spine surgery in WC patients are exacerbated in patients with anxiety and depression. WC patients with mental health comorbidities receive the least benefit from lumbar spine surgery and may represent the most vulnerable subset of patients with spine pathology. Addressing mental health comorbidities preoperatively may represent an opportunity for valuable resource allocation and surgical optimization in the WC population.