【Objective】Partial substitution of chemical fertilizer with organic fertilizer is an effective approach for the resource utilization of agricultural wastes in China. Nevertheless environmental exposure to veterinary antibiotics from livestock manure leads to the risk of environmental pollution. Antibiotics can limit the activity of soil microorganisms that play a pivotal role in carbon (C) and nitrogen (N) cycling within soil systems. However, the combined impact of soil antibiotic residue through the soil hydraulic erosion process on soil C and N loss of slope farmland remains unclear. A deep understanding of this mechanism is important for the prevention of nutrient loss and control of non-point source pollution of slope farmland in the Three Gorges Reservoir Area. 【Method】In this study, indoor hydraulic erosion experiments with artificial rainfall were conducted to simulate the process of 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; and 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 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 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 (NO– 3-N) loss by 29.68%, and ammonium nitrogen (NH+ 4-N) loss by 27.81%. The application of organic fertilizer with antibiotics exposure had 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, NO– 3-N and NH+ 4-N in organic fertilizer with antibiotics exposure replacing chemical fertilizer were significantly increased by 22.77% to 37.73%, 19.46% to 22.77% and 190.10% to 253.38%, respectively. Also, it was observed that antibiotics altered the microbial community structure of soil and sediment, which was probably 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 C and N loss, and only ENR exposure concentration had significant effects on TOC loss and NO– 3-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 22.77% to 37.73%, respectively. 【Conclusion】The 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 farmland.