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In wheat production, improving resource utilization and grain yield is the goal researcher have been pursuing. This study aimed to investigate if a regulated nitrogen (N) and selenium (Se) fertilizer management could increase wheat yield and N use efficiency (NUE). This study reports the effects of three N application levels (N0: 0 kg N ha⁻¹, N1: 180 kg N ha⁻¹, N2: 270 kg N ha⁻¹) and a combination of three Se application levels (Se0: 0 g Se ha⁻¹, Se1: 450 g Se ha⁻¹, Se2: 900 g Se ha⁻¹) on N metabolism, NUE and yield in wheat in 2020–2021. Compared with N0, wheat yield increased by 44.76% in N1 and by 54.32% in N2, and the activity of N-metabolizing enzymes increased by 25.15~35.03% in N1 and by 32.01~51.27% in N2. Compared with N1, the apparent recovery efficiency of N, the agronomic N use efficiency and the partial factor productivity of applied N decreased by 15.71%, 28.00% and 28.93% in N2, respectively. Compared with Se0, the 1000-grain weight increased by 3.93% in Se1 and by 4.87% in Se2, and the activity of nitrogen-metabolizing enzymes increased by 4.23~4.91% in Se1 and by 6.65~8.46% in Se2. We conclude that Se could improve the wheat 1000-grain weigh and N metabolism and has the potential to increase wheat yield and NUE.