The planting of seedlings is the most effective measure for vegetation restoration. However, this practice is challenging in desert ecosystems where water and nutrients are scarce. Calligonum mongolicum is a sand-fixing pioneer shrub species, and its adaptive strategy for nitrogen (N) deposition and drought is poorly understood. Thus, in a pot experiment, we studied the impacts of four N levels (0, 3, 6, 9 gN·m−2·year−1) under drought or a well-watered regime on multiple eco-physiological responses of 1-year-old C. mongolicum seedlings. Compared to well-watered conditions, drought considerably influenced seedling growth by impairing photosynthesis, osmolyte accumulation and activity of superoxide dismutase and enzymes related to N metabolism. Nitrogen addition improved the productivity of drought-stressed seedlings, as revealed by increased water use efficiency, enhanced superoxide dismutase and nitrite reductase activity and elevated N and phosphorus (P) levels in seedlings. Nevertheless, the addition of moderate to high levels of N (6–9 gN·m−2·year−1) impaired net photosynthesis, osmolyte accumulation and nitrate reductase activity. N addition and water regimes did not markedly change the N:P ratios of aboveground parts; while more biomass and nutrients were allocated to fine roots to assimilate the insufficient resources. Soluble protein in assimilating shoots might play a vital role in adaptation to the desert environment. The response of C. mongolicum seedlings to N addtion and drought involved an interdependency between soluble protein and morphological, physiological and biochemical processes. These findings provide an important reference for vegetation restoration in arid lands under global change.Fil: Zhang, Z.. Chinese Academy of Sciences; República de China. Cele National Station of Observation and Research for Desert-Grassland Ecosystems; ChinaFil: Tariq, A.. Chinese Academy of Sciences; República de China. Cele National Station of Observation and Research for Desert-Grassland Ecosystems; ChinaFil: Zeng, F.. Chinese Academy of Sciences; República de China. Cele National Station of Observation and Research for Desert-Grassland Ecosystems; ChinaFil: Chai, X.. Chinese Academy of Sciences; República de China. Cele National Station of Observation and Research for Desert-Grassland Ecosystems; ChinaFil: Graciano, Corina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Fisiología Vegetal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Fisiología Vegetal; Argentin