A mathematical model is developed to analyze a single-effect thermal vapor compression (TVC) desalination system. The effects of the variation of operation conditions such as the intake seawater temperature and the mass flow rate of cooling water on the system performance are investigated for a specific desalination unit. The system performance is found to decrease when the intake seawater temperature is different from the design value. By adjusting the mass flow rate of cooling water, a better system performance can be obtained when the intake seawater temperature differs from the design conditions. Decreasing the cooling water flow rate to values lower than the design value can lead to a better performance when the intake seawater temperature is lower than the design value, and the system performance reaches a peak point when the cooling water flow rate decreases to a definite level. A better performance can also be obtained by increasing the cooling water flow rate to values higher than design value, when the intake seawater temperature is higher than the design value and the system performance also reaches a peak point when the cooling water flow rate increases to a definite level.