ABSTRACT Aim We aimed to investigate the effects of erythropoietin, acetyl-l-carnitine, and their combination on nerve regeneration in experimental peripheral nerve injury. Methods Rats were randomly divided into five groups – sham-operated (S), sciatic nerve crush injury (C), C + acetyl-l-carnitine (ALCAR), C + erythropoietin (EPO), and C + EPO + ALCAR. ALCAR (50 mg/kg/day) was administered intraperitoneally, and EPO (5000 U/kg) was injected subcutaneously for 10 days. Functional recovery was evaluated using walking track analysis (sciatic functional index [SFI]), somatosensory evoked potentials (SEPs), thiobarbituric acid reactive substance (TBARS) assay, and caspase-3 and S100 immunoreactivities. Results In SFI analyses, delayed functional recovery was observed in the C group, whereas the functional recovery of rats treated with EPO and ALCAR significantly improved. The latencies of the SEP components were significantly prolonged in C group. In the treatment groups (C + EPO, C + ALCAR, and C + EPO + ALCAR), all recorded values of SEP components significantly decreased. TBARS levels in C group were significantly higher than those in the S group. EPO and ALCAR administration significantly decreased TBARS levels. Caspase-3 immunoreactivity was increased in the C group, whereas it was decreased in the treatment groups. S100 immunolabelling was significantly decreased in the C group. EPO and ALCAR administration caused an increase in the amount of S100-positive cells in all treatment groups. Conclusion EPO and ALCAR administration could accelerate sciatic nerve repair by reducing apoptosis and lipid peroxidation and promoting myelinization. Although both EPO and ALCAR had positive effects on nerve healing, their combined efficacy had no statistically significant effect on peripheral nerve regeneration.