Chronic kidney disease (CKD), a prevalent condition in older cats, is characterized by progressive and irreversible renal damage. Early detection is crucial for timely intervention, potentially slowing disease progression and extending the lifespan of affected cats. The study related to these datasets aimed to identify novel, non-invasive protein biomarkers for early detection of feline CKD. MS-based proteome profiling was employed to analyze serum samples from CKD-affected and healthy control cats across two independent cohorts.