Abstract This study aimed at assessing the impact of some wells abiotic factors on the antimicrobial susceptibility of Pseudomonas aeruginosa isolated. A total of 14 well waters of Douala and Yaoundé towns (Cameroon, Central Africa) were chosen. Fifteen antibiotics were used to test antimicrobial susceptibility with the majority belonging to β-lactam, aminoglycoside and quinolone groups. Result showed that in Douala, electrical conductivity of water ranged from 145.38 to 559.69 μS/cm in well, while in Yaoundé, it ranged from 172.5 to 710.2 μS/cm. Dissolved oxygen ranged from 2.5 to 5.5 mg/l and from 3.9 to 5.1 mg/l, respectively, in Douala and Yaoundé. Organic matter varied from 2.3 to 7.2 mg/l and 1.4 to 5.2 mg/l in Douala and Yaoundé, respectively. As for pH, it fluctuated between 5.56 and 6.66 CU and between 5.1 and 7.0, respectively, in Douala and Yaoundé. The sampled waters harbour multi-drug-resistant P. aeruginosa strains. About 20.40% of strains from wells in Yaoundé metropolis expressed resistance to at least 5 antibiotics, whereas from wells in Douala town, up to 33.33% of strains were resistant to at least 8 antibiotics including ticarcillin, ceftazidime and gentamicin. The effect of abiotic factors on the sensitivity to antibiotics was assessed using the multiple regression tests. In both towns, less than 5% in the changes of physicochemical parameters of well waters explained the variance in inhibition diameter values of antibiotics (p ≤ 0.05). The pH significantly impacts on antimicrobial susceptibility. Environmental conditions are less stressful for P. aeruginosa and fairly affect its antimicrobial susceptibility.