Upgrading the efficiency of native soil nitrogen (N) and balancing the N derived from soil and fertilizers under drip irrigation with low-quality water is crucial for reducing N application and curtailing environmental degradation in arid regions. In this study, a control experiment with four N (N-15-labeled urea) rates of 0 (F0), 255 (F1), 315 (F2) and 375 kg center dot ha(-1) (F3) was established by applying groundwater (Q1, 1.27 g center dot l(-1)), brackish water (Q2, 3.03 g center dot l(-1)) and saline water (Q3, 4.90 g center dot l(-1)) to differentiate cotton (Gossypium hirsutum L.) uptake from native soil N and fertilizer N by 15N tracer technology. The results indicated that increasing water salinity increased the soil salt content and significantly reduced cotton biomass. The cumulative utilization percentages of soil N (CUSN) and fertilizer N (CUFN) ranged from 7.4% to 14.1% and 35.9-54.5%, respectively, during the growing season. The CUFN decreased with increasing irrigation water salinity. Appropriate nitrogen fertilizer alleviated the salt stress on N uptake. The N rate of 315 kg center dot ha(-1) promoted soil N and fertilizer N uptake and produced higher percentages of utilization of soil N (PUSN) and fertilizer N (PUFN) during the squaring and flower boll stage under Q1 and Q2 irrigation. An N rate of 375 kg center dot ha(-1) significantly increased PUSN under Q3 irrigation, particularly during the mature stage. In addition, high salinity water and N rates caused a larger fertilizer N loss. Considering cotton growth and balance between soil N and fertilizer N, an N rate of 315 kg center dot ha(-1) was suitable for cotton under mulched drip irrigation when applying Q1 and Q2 in arid regions, and 375 kg center dot ha(-1) was recommended for Q3 irrigation. The appropriate addition of nitrogen fertilizer during the flower boll stage will promote cotton growth under brackish water.