Abstract Loneliness is an increasingly recognized public health concern in the United States, particularly among individuals with spinal cord injury (SCI). While leisure travel has the potential to alleviate loneliness, the underlying mechanisms remain unclear. Given that leisure travel can also foster social interaction (SI), this study examined differences in SI and loneliness between active and inactive travelers with SCI and tested the mediating role of SI. Results indicated that inactive travelers reported significantly lower levels of SI and higher levels of loneliness compared to active travelers. Leisure travel participation was positively associated with SI (β = 2.43, p < 0.001) and negatively associated with loneliness (β = −0.85, p < 0.001). Additionally, SI was significantly correlated with lower loneliness scores (β = −0.08, p < 0.001), mediating 18.42% of the total effect. Findings highlight leisure travel’s role in enhancing SI and reducing loneliness among people with SCI.