Body fluid homeostasis undergoes significant changes during hypokinesia (diminished movement). Understanding of fluid transfer between body fluid compartments and its regulating mechanisms was the aim of this study for disclosing impaired fluid retention during hypokinesia (HK). Studies were done on 12 male Macaca mulatta (rhesus monkeys) aged three to five years (5.15 to 6.56 kg) during 90 days period of pre-HK and 90 days period of HK. All primates were divided equally into two groups: vivarium control primates (VCP) and hypokinetic primates (HKP). Hypokinetic primates were kept for 90 days in small individual cages that restricted their movements in all directions without hindering food and fluid intakes. Control primates were housed in individual cages without their movements being restricted. Total body fluid (TBF), intracellular fluid volume (IFV) and circulating plasma volume (CPV) decreased significantly (p < 0.05), while extracellular fluid volume (EFV) and interstitial fluid volume (IsFV) decreased significantly (p < 0.05) at the initial seven days of the HK period and after the 7th day increase progressively in HKP compared with their pre-HK values and their respective control values in VCP. Fluid excretion, urinary and plasma sodium (Na) and potassium (K) levels increased significantly (p < 0.05), while fluid intake and fluid retention decreased significantly (p < 0.05) in HKP compared with their pre-HK values and their respective controls in VCP. The measured parameters did not change in VCP compared with their pre-HK values. It was concluded that decreased IFV and CPV may demonstrate fluid depletion, while marked increase of fluid loss despite of fluid depletion may demonstrate impair fluid retention during HK. Dissociation between fluid loss and fluid depletion may demonstrate the presence of reduced fluid retention as the mechanism of development of fluid depletion during HK.