Background: Recent evidence suggests that increasing dietary intake of minerals reduces the risk of dementia. This study aimed to examine the relationship between potassium and diagnosis of mild cognitive impairment (MCI) in a sample of older Mexican-Americans from rural and urban populations. Methods: The sample was formed of a total of 139 participants with MCI and 371 normal controls from two independent cohorts: a rural cohort (Facing Rural Obstacles to Healthcare Now through Intervention, Education and Research Project FRONTIER) and an urban cohort (the Health and Aging Brain among Latino Elders HABLE study). Serum electrolytes examined were sodium and potassium. Age and education were entered in the model as covariates. Results: Across both cohorts, the Project FRONTIER (OR = 3.1; p = 0.01) and the HABLE Project (OR = 2.0; p = 0.04), the results indicated that serum potassium levels significantly increased the risk of diagnosis of MCI. Conclusion: Our finding suggested a link between serum potassium levels and a diagnosis of MCI in Mexican-Americans. The results of this study support a previous research which has suggested that the risk factors for MCI may vary by ethnicity.