Background: Life functions depend on electrolytes. Life-threatening complications can occur when electrolyte disorders disrupt normal bodily functions. Recent reports have linked immune checkpoint inhibitors (ICIs) with electrolyte disorders. Due to this, ICIs need to be evaluated for their impact on electrolyte balance. Methods: In this study, adverse reaction reports for ICIs were analyzed using data from the FAERS database between 2012 and 2023. In order to identify adverse events related to electrolyte disorders caused by ICIs, disproportionality analysis was used.The study provided a comprehensive depiction of the characteristics of adverse event reports pertaining to electrolyte imbalances linked to ICIs, as documented in the FAERS database. Factors influencing the outcomes were examined through univariate logistic regression analysis. Furthermore, potential biological pathways associated with ICIs-related electrolyte disorders were explored by leveraging data from The Cancer Genome Atlas (TCGA). Lastly, the expression levels of ICIs in diverse organs, tissues, and cells were scrutinized to evaluate the occurrence of tumor type-specific immune-related adverse events (irAEs). Results: Adverse events related to electrolyte disorders were reported in 1.9% of all adverse event reports for ICIs documented in the FAERS database. These electrolyte disorders were categorized into five distinct types, collectively referred to as electrolyte disorder adverse events (EDAEs) associated with ICIs. The reports involving ICI-related EDAEs exhibited a median age of 66, with 18% of these cases resulting in fatalities. Typically, the onset of EDAEs occurred around day 41, with a majority of cases manifesting within the initial two months. Upon analyzing variables influencing EDAEs, we observed that male patients exhibited a 16% lower likelihood of experiencing ICI-related EDAEs compared to their female counterparts (OR = 0.84 [0.75-0.94], P = 0.003). Notably, ICI-induced EDAEs demonstrated a potential association with thyroid hormone transport (R = 0.63, p= 7.07e−03). In humans, the expression of PD-1, PD-L1, and CTLA-4 genes was particularly pronounced in the lungs and spleen. Interpretation: The study meticulously investigated the incidence of electrolyte disorder side effects closely associated with ICI therapy, while also exploring the influencing factors and potential underlying biological mechanisms. These findings hold significant relevance for future research endeavors and medical practices within this domain.