Purpose: The possibility that the sympathetic nervous system (SNS) controls bone remodeling has been raised; however, the actual function of the SNS in osseointegration is still unknown. This study aimed to investigate the effect of chemical sympathectomy on peri-implant osseointegration in adult mice. Materials and Methods: Forty C57BL/6J mice (8-week-old) were divided into two groups: a sympathectomy group and a control group, which were administered 6-hydroxydopamine and saline, respectively, by intraperitoneal injection for 5 days. Then, the mice were exposed to implant surgery. Analyses of serum chemistry, microcomputed tomography, biomechanical test, and bone histomorphometry were employed at 2 and 4 weeks. Results: Compared with the control, the chemical sympathectomy group had a higher serum level of C-terminal collagen I cross-links but lower serum osteocalcin. After 4 weeks, peri-implant trabecular microstructure, including trabecular volume, trabecular thickness, the percentage of osseointegration, and bone-to-implant contact, was lower; however, the trabecular separation was higher in the sympathectomy group mice in comparison with the control group. In addition, the strength of bone-titanium integration measured by the biomechanical resistance test was lower. Furthermore, histomorphologic evidence revealed that the osteoclast counts were higher in the sympathectomy group, while the mineral apposition rate and the bone formation rate per bone surface were significantly lower. Conclusion: Within the limitations of this experimental study, the data showed that chemical sympathectomy has a negative effect in peri-implant osseointegration, suggesting that the SNS may need to be taken into consideration in terms of peri-implant bone healing. Keywords: chemical sympathectomy, implant, osseointegration, sympathetic nervous system