Background: PD-L1 expression is predictive of response to treatment with PD-1/PD-L1 immune checkpoint inhibitors (ICI) among patients with metastatic non-small cell lung cancer (mNSCLC). Brain metastases (BM) are common in patients with mNSCLC and carry significant morbidity. While the use of ICI has significantly improved survival for mNSCLC, it is unclear if patients with brain metastases have the same survival benefit. Methods: In this retrospective study, we reviewed data from all patients treated at our center with mNSCLC who had PD-L1 testing from 2015-2019. Patients with another active malignancy were excluded. Descriptive statistics were calculated using proportions and means using SAS v9.4. We examined the relationship between PD-L1 level ( < 50% vs ≥50%) and BM at diagnosis among patients with mNSCLC using chi-square analysis. We then compared overall survival (OS) and progression free survival (PFS) among mNSCLC patients with and without BM at diagnosis treated with ICI using Kaplan-Meier plots followed by log rank tests. Results: 141 mNSCLC patients with PD-L1 results were identified. 71 (50.4%) were female. Mean age was 63. 71 (50.4%) were current smokers, 53 (37.6%) were former smokers. Histology included 111 (78.7%) adenocarcinoma, 19 (13.5%) squamous cell carcinoma, and 11 (7.8%) other or mixed types. 19 (13.5%) had KRAS mutation, 13 (9.2%) had EGFR mutation, 1 had ALK rearrangement, 3 had ROS1 rearrangement, and 2 had BRAF mutations. 86 (61.0%) were PD-L1 high (≥50%). 57 (40.4%) had BM at diagnosis. Patients with high PD-L1 had a higher rate of BM at diagnosis (47.3% vs 36.0%), but this trend was not statistically significant (p = 0.18). There were significantly more current smokers among those with BM at diagnosis than those without BM (p = 0.01). Among patients treated with first line ICI (n = 78), median OS was 26.5 months for those without BM and 12.2 months for those with BM at diagnosis, although this difference was not significant (p = 0.11). Median PFS was 8.9 months for patients without BM and 8.6 for those with BM (p = 0.58). Conclusions: While a higher proportion of patients with high PD-L1 had BM at the time of metastatic diagnosis, this trend was not significant. Among patients treated with ICI, survival for those with or without BM at the time of diagnosis was not significantly different. Our observations may be limited by the number of patients.