Background: The mini-fluid challenge test is a good predictor and has minimal limitations in determining fluid responsiveness in the critically ill. However, it primarily relies on colloid infusion. The availability of colloids may vary among hospitals in resource-limited countries, and they can be more expensive than crystalloid fluids. Objective: The study aimed to use crystalloids instead of colloids to predict fluid responsiveness. Methods: This study was conducted from August 2022 to February 2023 among patients with shock in the medical ICU to assess fluid responsiveness. Arterial and central venous catheters were used for the intravenous infusion and monitoring. Data were collected during two consecutive crystalloid mini-fluid challenges of 50 mL each in 1 minute, 100 mL in 2 minutes, and a standard fluid challenge of 300 mL over 15 minutes. The objective was to predict a stroke volume index (SVI) increase of > 10%. Diagnostic accuracy was evaluated using the Receiver Operating Characteristic (ROC) curve, and hemodynamic variables in the positive fluid challenge group were compared for different volume expansions. Results: Twenty-nine patients (62% males; median age, 75 years) were included, with 42 fluid challenge test events. Septic shock was the primary condition in 83% of the cases. The 50 mL crystalloid mini-fluid challenge showed an accuracy of 80% with a sensitivity of 69% and specificity of 100% at the cutoff level of SVI > 5%, Area Under ROC (AUROC)=0.79. In comparison, the 100 mL crystalloid mini-fluid challenge demonstrated an accuracy of 85% (sensitivity of 79% and specificity of 100%) at the cutoff level of SVI > 10% (AUROC= 0.89). In the positive fluid challenge group, administration of crystalloids led to a significant increase in mean arterial pressure and SVI, while other parameters remained comparable. Conclusions: A mini-fluid challenge test with 100 mL crystalloids can predict fluid responsiveness in critically ill patients. The best cutoff level was a change in SVI > 10% from baseline.