In this study, the interactive effects of soil moisture and S levels were investigated on alfalfa (Medicago sativa c. v Garehyounjeh) shoot and root fresh weights, water use efficiency (WUE), and concentrations of some elements in a loam soil under greenhouse conditions. A factorial experiment based on a randomized complete blocks design with three replications was conducted with two factors: soil moisture at three levels (0. 81 FC– FC, 0. 56– 0. 75 FC, and 0. 35– 0. 50FC) and SS at four levels (0, 15, 30, and 60 g/kg soil). When 10% of the alfalfa plants flowered, the shoot and root fresh weights, concentrations of nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), sodium (Na), copper (Cu), iron (Fe), manganese (Mn), and zinc (Zn) and WUE of alfalfa plant were measured. The results showed that the main and interactive effects of SS and soil moisture on alfalfa shoot and root fresh weights, WUE, and concentrations of elements were significant (p≤ 0. 01). The decrease in soil moisture content, decreased alfalfa shoot and root fresh weights, WUE, concentrations of Fe in the shoot and concentrations of P, Fe, and Na in the root (p≤ 0. 05); while it increased concentrations of Cu in the root, and Cu and Zn in the shoot (p≤ 0. 05). Effect of soil water content on concentrations of N, K, Ca, Mg, Zn, and Mn of the root depended on the level of SS. Concentrations of Mg, Fe, Zn, Cu, and Mn in the root and shoot and concentrations of P, K, and Ca in the root were increased (p≤ 0. 05) with the use of SS and increase in its level. By increasing the SS level, shoot and root fresh weights were initially increased and then decreased (p≤ 0. 05). Effect of SS on WUE depended on soil water content. With sufficient water supply (0. 81FC– FC), WUE was increased with increment of SS level, while under water-deficit stress (0. 35FC– 0. 50FC), application of SS up to 30 g/kg increased WUE but at the level of 60 g/kg, increase in the soil salinity reduced WUE (p≤ 0. 05). To increase WUE and improve the nutrition and growth of alfalfa at similar conditions, 30 grams of SS per kilogram of soil may be recommended under both well-watered and water-deficit conditions. Although the use of sewage sludge had some beneficial effects in this experiment, the potential risks of heavy metals in longterm application of this organic waste should be considered and avoided.