Updated project metadata. Due to multifactorial reasons, such as decreased thirst and decreased total body water, elderly patients are vulnerable to dehydration. The study aims to investigate whether moderate dehydration or hyperhydration affects the blood proteome. Blood samples, medication and bioelectrical impedance analysis (BIA) details were collected from 131 geriatric patients (77 women, 54 men). Based on an evaluation by Bioelectrical Impedance Vector Analyses (BIVA) of this cohort, for each hydration status (dehydrated, hyperhydrated and control), five appropriate blood serum samples for both male and female were analyzed by LC-MS. Overall, 262 proteins for female patients and 293 proteins for male patients could be quantified. 38 proteins had significantly different abundance, showing that hydration status does indeed affect the serum proteome. Protein enrichment analysis of the affected proteins revealed “Wound Healing” and “Keratinization” as the two main biological processes being dysregulated. Especially, proteins involved in clot formation are affected by hydration status.