Background: High baseline neutrophil to lymphocyte ratio (NLR) is associated with inferior OS for patients with stage III/IV NSCLC pts treated with nivo or pembro. This study evaluates potential relationships between baseline and longitudinal NLR and absolute LCs with PFS and OS in aNSCLC pts on nivo or pembro. Methods: Patients with stage III/IV NSCLC who received at least one cycle of nivo or pembro between January 2015 and January 2017 were identified in our pharmacy database. Pt demographics, longitudinal leukocyte counts, treatment start date, date of progression, and last follow-up were recorded. OS and PFS were assessed by log-rank tests and Cox proportional hazard analysis. Time-dependent Cox model based analyses were used to assess association with longitudinal NLR and LCs. A cutoff of NLR 5.0 was used for NLR. Results: The study included 162 aNSCLC pts. Median age 68 yrs, male/female 40.1%/59.9%. NLR > 5.0 was associated with inferior PFS longitudinally. Median PFS values were: baseline NLR > 5/ < 5 = 2.1/3.9 mos (p = 0.03), at 6 wks NLR > 5/ < 5 = 2.6/6.1 mos (p = 0.003), at 12 wks NLR > 5/ < 5 = 3.8/7.1 mos (p = 0.03). NLR > 5.0 was similarly associated with inferior OS at the same intervals. In time-dependent analyses, NLRs as a continuous variable were associated with inferior PFS (HR 1.03, p = 0.02) and OS (HR 1.05, p < 0.001). Longitudinal analyses of LCs as a continuous variable showed that higher LCs over time were associated with superior PFS (HR 0.49, p = 0.0083) and OS (HR 0.357, p = 0.006). Conclusions: Low baseline and longitudinally lower NLRs are associated with longer PFS and OS in aNSCLC pts on nivo or pembro. High baseline and longitudinally higher LCs were associated with superior PFS and OS in the same group. While NLRs and LCs may merely be prognostic indicators, it’s possible that they reflect a patient’s ability to mount an immune response. They may also be useful in guiding strategies to overcome immunotherapy resistance.