History and Objectives: Considering the significance of plasma osmolality as an appropriate indicator of water and electrolyte balance, its importance as a stimulus and the extent of its difference with real osmolality, this study was carried out to determine plasma osmolality and its measurement in infants under fluid therapy in selected hospitals in Isfahan.

Materials and Methods: The cross-sectional protocol of this study was carried out on 45 infants at an age of 1-10 days in wards of special care for infants. Plasma osmolality was measured using direct method and also through measuring sodium, potassium, glucose and BUN concentrations. Then, paired t-test was applied regarding weight and degree of attention.

Results: The measured osmolality was 260.57±1.84 mosmol/kg and was significantly different from the predicted one. These findings were also correct for infants with weights higher than 2500g.

Conclusion and Recommendations: The above-mentioned method can correctly measure plasma osmolality as direct method. It is concluded to use in order of importance direct method and then mathematical method for measurement of plasma osmolality.