Background: Lung cancer-related inflammation is associated with depression. Both elevated inflammation and depression are associated with worse survival. However, outcomes of patients with concomitant depression and elevated inflammation are not known. Materials & methods: Patients with metastatic lung cancer (n=123) were evaluated for depression and inflammation. Kaplan-Meier plots and Cox proportional hazard models provided survival estimations. Results: Estimated survival was 515days for the cohort and 323days for patients with depression (hazard ratio: 1.12;95% CI: 1.05-1.179), 356days for patients with elevated inflammation (hazard ratio: 2.85, 95% CI: 1.856-4.388), and 307days with both (χ2=12.546; p< 0.001]). Conclusion: Depression and inflammation are independently associated with inferior survival. Survival worsened by inflammation is mediated by depression-a treatable risk factor.