BACKGROUND: Direct colloid osmometry provides an objective assessment of the oncotic effects of crystalloid or colloidal fluid therapy, which is especially useful in monitoring fluid therapy of critically ill camelids due to their tendency toward nonspecific hypoproteinemia with increased risk of developing edema and ascites. OBJECTIVES: The aims of this study were to measure colloid osmotic pressure (COP) of alpacas and llamas, determine its correlation with concentrations of total protein (TP) and total solids (TS), as well as both albumin (A) and globulin (G) concentrations in the same model (A+G), and evaluate the effects of sample type and storage conditions on COP. METHODS: Blood was collected from clinically healthy alpacas (n=23) and llamas (n=22) into heparin tubes. COP of fresh whole blood (COP(FB) ) and plasma (COP(FP) ) was determined using a membrane osmometer. For 20 alpacas, COP of refrigerated whole blood (COP(RB) ) and frozen plasma (COP(FrP) ) was also measured. Correlations between COP(FB) and TS, TP, and A+G concentrations were assessed by simple and multiple regression analysis to model potential predictors. RESULTS: Median COP(FB) from alpacas (24.6 mmHg, range 19.3-28.1) was not significantly different from that of llamas (25.3 mmHg, range 22.5-33.7). Sample type or storage conditions did not affect COP. Measured COP had a strong positive linear correlation with TS, TP, and A+G concentrations in alpacas (r(2) =.7, .74, and .88, respectively). In llamas, COP correlated best with TS concentration (r(2) =.59), whereas correlation with TP and A+G concentrations was poor (r(2) =.19 and .25, respectively). CONCLUSION: COP can be measured using heparinized whole blood or plasma, either fresh or stored. Direct measurement is recommended whenever quantitative knowledge of COP is required in clinical or research setting. Further studies are needed to verify if the poor association of COP with TP found in this study can be generalized to llamas.