Background: C-Reactive Protein (CRP) is an acute phase reactant which is elevated in inflammatory conditions and malignancy. Elevated CRP levels are associated with poor prognosis in many cancers and has been reported in patients with melanoma treated with ICI. We examined the association between CRP levels during therapy with ICI in patients with advanced lung cancer and radiological response. Methods: A retrospective study of patients with metastatic lung cancer (stage IV) who were treated with immunotherapy from 2016 to 2019 was conducted. CRP levels were checked at or soon after initiation of therapy and at frequent intervals thereafter. Association between CRP levels and response was determined. Results: 36 patients had initial (at the beginning of therapy, baseline) and subsequent CRP levels recorded during the first course of immunotherapy. Among the 36 patients, 16 (44%) had radiological response or stable disease, and 20 (55%) had radiological progression. The median age was 69 years (range 50 – 89 years); male/female 35/1, Caucasian/African American/other 26/9/1. There was no significant difference in distribution of initial CRP levels between patients with response vs progression as assessed by Kruskal-Wallis test (P-val: 0.20). Logistic regression modeling was employed to examine the association between final CRP level, the last measurement while on ICI therapy (adjusted for baseline CRP level) and odds of observing a response. A unit increase in final CRP level was associated with 4% decrease in odds of observing a response (Odds Ratio, 95% CI: 0.96, 0.92-1.00, P-val: 0.05). Conclusions: Baseline-adjusted final CRP levels were inversely associated with likelihood of observing a response in advanced lung cancer subjects treated with ICI. Further validation in prospective studies is warranted.