e24146 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Cancer patients, especially lung cancer (LCa), are at an increased risk of developing electrolyte imbalance due to several etiologies such as poor nutrition, paraneoplastic syndromes, etc. It is vital to address electrolyte disturbances with the use of ICIs. Objective: The study aims to understand the relationship between ICIs and electrolyte disturbance in LCa patients. Methods: TrinetX, a global federated research network, provides a dataset of electronic medical records from different healthcare organizations (HCOs), was utilized. Initial query was made to isolate patients with LCa stages 2-4. The 2 groups were based on the presence or absence of IO (atezolizumab, durvalumab, pembrolizumab, nivolumab, ipilimumab). Further, propensity score matching (PSM) was carried out to match age, sex, race, chronic kidney disease, diarrhea. Compare outcome analytic function was utilized to map the co-relation with electrolyte imbalance. Results: 41,818 patients were identified, out of which 12.37% (n = 5172) patients received immunotherapy at some point in their cancer treatment. There was no statistical difference in age (65.9 ± 10.3 vs 65.9 ± 11.3, p = 0.8608) as well as gender in both groups. Caucasians (69% vs 66% for Causians (p < 0.0001)) were the predominant race in both groups and were more likely to receive immunotherapy compared to African Americans (12% vs 14% in AA (p = 0.0004)). Diarrhea (30% vs 9%, p < 0.0001) and Chronic kidney disease (CKD) (18% vs 8%, p < 0.0001) were predominantly seen in IO group. Prior to matching, hypomagnesemia (HypoMg) (10.47% vs 5.85%, p < 0.0001), hypocalcemia(HypoCa) (3.36% vs 2.03%, p < 0.0001), hypokalemia (HypoK) (16.91% vs 11.02%, p < 0.0001), hyperkalemia (HyperK) (7.69% vs 4.88%, p < 0.0001), hyponatremia (HypoNa) (16.82% vs 10.66%, p < 0.0001) and hypercalcemia (HyperCa) (5.26% vs 3.05%, p < 0.0001) were seen higher in IO group while hypermagnesemia (HyperMg) (2.04% vs 2.62%, p = 0.0150) was more seen in the non IO group, with no significant difference in hypernatremia (HyperNa) (2.34% vs 1.95%, p = 0.0634). After PSM, HypoMg (10.48% vs 7.01%, p < 0.0001), HypoK (16.92% vs 12.64%, p < 0.0001), HyperK (7.69% vs 6.26%, p = 0.0060), HypoNa (16.80% vs 11.56%, p < 0.0001) and HyperCa (5.26% vs 3.06%, p < 0.0001) were seen more in IO group, while HyperMg (2.04% vs 2.67%, p = 0.0399) was higher in non IO and there was no significant difference for HypoCa (3.36% vs 2.77, p = 0.0829) and HyperNa (2.34% vs 1.89%, p = 0.1135). Conclusions: Our study demonstrated that there is correlation between ICI use and electrolyte imbalance. Providers should be vigilant about the potential electrolyte abnormalities when treating patients with ICI therapy.