【Objective】Partial substitution of chemical fertilizer with organic fertilizer is an effective approaches for the resource utilization of agricultural wastes in China, while environmental exposure of veterinary antibiotics from livestock excreta leads to the risk of environmental pollution. Antibiotics can limit the activity of soil microbial, which the soil microorganisms play a pivotal role in carbon (C) and nitrogen (N) cycling within soil systems. However, the combined the impact of soil antibiotic residue through soil hydraulic erosion process on soil C and N loss of slope cultivated land is not clearly. A deeply understanding this is important for prevention nutrients loss and control of non-point source pollution of slope cultivated land in the Three Gorges Reservoir Area. 【Method】In this study, the indoor hydraulic erosion experiments with artificial rainfall were conducted to simulate the process of the antibiotics impact on C and N erosion Loss, and five treatments were set up: 1) CK, no fertilization control; 2) NP, only chemical fertilizer; 3) OMNP, organic fertilizer substituting 30% chemical phosphorus fertilizer; 4) OMNPT, oxytetracycline (OTC) contaminated organic fertilizer substituting 30% chemical phosphorus fertilizer; 5) OMNPQ, enrofloxacin (ENR) contaminated organic fertilizer substituting 30% chemical phosphorus fertilizer. 【Result】The results showed that: (1) Compared with the application of chemical fertilizer, partial substitution of chemical fertilizer with organic fertilizer has significantly reduced the hydraulic erosion of slope land; however, organic fertilizer with antibiotics exposure had no significant effect on erosion process compared to OMNP. (2) The residual concentrations of OTC and ENR in soil were 32.30 μg·kg-1 and 25.55 μg·kg-1, respectively. OTC loss was dominated by runoff (loss mass, 178.60 μg), while ENR loss was dominated by sediment (loss mass, 79.18 μg). (3) Compared with the application of chemical fertilizer only, partial substitution of chemical fertilizer with organic fertilizer has significantly reduced total organic carbon (TOC) loss by 8.94% to 11.54%, mineral-associated organic carbon (MAOC) loss by 11.23% to 13.97%, total nitrogen (TN) loss by 22.00%, nitrate nitrogen (NO3--N) loss by 29.68%, and ammonium nitrogen (NH4+-N) loss by 27.81%, respectively. The application of organic fertilizer with antibiotics exposure has no significant effect on the loss of TOC, dissolved organic carbon (DOC), particulate organic carbon (POC) and MAOC, but increased the risk of soil N loss. Compared with the organic fertilizer without antibiotics, the loss fluxes of TN, NO3--N and NH4+-N in organic fertilizer replacing chemical fertilizer were significantly increased by 22.77% to 37.73%, 19.46% to 22.77% and 190.10% to 253.38%, respectively. Antibiotics alter the microbial community structure of soil and sediment, which may be the main cause of increased soil nitrogen loss during erosion processes. (4) Pearson correlation analysis revealed that antibiotic exposure suppressed bacterial abundance and microbial biomass carbon (MBC), and promoted C and N loss. However, the two antibiotics had different effects on soil carbon and nitrogen loss, and only ENR exposure concentration has significant effects on TOC loss and NO3--N loss. Compared with the application of organic fertilizer without antibiotics, antibiotics (OTC and ENR) increased the proportion of soil C and N loss by 0.80% to 2.94% and TN by 22.77% to 37.73%. 【Conclusion】In summary, partial substitution of chemical fertilizer with organic fertilizer can reduce soil erosion and nutrient loss of slope land. However, this action may also result in the contamination of soil with antibiotics, which could subsequently lead to the increased nitrogen loss of slope cultivated land.