The aim of the present study was to explore the prevalence and potential risk factors associated with infestation by Psoroptes spp. mites in buffalo at smallholder farms in the Nile Delta region, Egypt. A total of 318 out of 1234 buffalo in 77 small scale herds were examined. The age of buffalo varied from three months to seven years. In all, 53 (16.66%) buffalo were recorded to be infested; 51 (16.35%) with Psoroptes spp. mites and two cases (0.31%) with Chorioptes spp. mites. Multivariate logistic regression was performed for significant risk factors at univariate analysis on both animal and herd level. The results of multivariate analysis showed that, on the animal level, the prevalence was affected by animal age (P < 0.01; OR: 0.71; CI 95%: 0.441-1.11), season (P < 0.01; OR: 1.20; CI 95%:0.541-1.15), indoor management (P < 0.001; OR: 6.625; CI 95%:2.489 -17.631) and rearing with other animals (P < 0.01; OR: 2.22; CI 95%:1.340 -7.132). However, on the herd level, the prevalence was affected by indoor rearing (P < 0.05; OR: 22.4; CI 95%:2.75-16.431), mixed rearing with other animal species (P < 0.05; OR: 4.5; CI 95%:1.66-7.941), and season (P < 0.01; OR: 2.3; CI 95%:0.575-2.426). Clinically, mild skin lesions with mild pruritus were significantly prevalent in buffalo with the infestation by Psoroptes spp. mites (P < 0.001), where 33/51 cases showed mild lesions. Also, psoroptic mites had significant association with inappitence (P < 0.001). The result of the present study indicates that Psoroptes spp. mites are the most prevalent in buffalo in the Nile Delta Region, Egypt. Moreover, recognition of risk factors associated with mange mites in buffalo may enable the practitioner to establish the most appropriate control measures.