Background Companion animals; dog and cat are closely associated with the daily life of humans and may be implemented in the transmission of many microorganisms to their adopters. Pseudomonas aeruginosa (P. aeruginosa) is a suited opportunistic and harsh to treat pathogen due to its rife environmental distribution, unique intrinsic and acquired resistance to numerous antimicrobials’ categories. Objective The current study targeted to survey the existence of P. aeruginosa in laboratory samples obtained from diseased dogs and cats. The study also investigated the susceptibility and resistance of recovered isolates against antimicrobials. Materials and methods A total of 315 samples gathered from veterinary laboratories in Great Cairo governorates; fecal, ear, eye, respiratory, wounds and urine samples were previously collected from diseased dogs and cats. The samples were examined bacteriologically and biochemically to isolate P. aeruginosa. The isolates were assayed for their sensitivity and resistance versus 25 antimicrobials belonging to various categories. Results and conclusion Fifty- eight P. aeruginosa isolates (18.41%) were obtained from 315 dogs (44/233, 18.88%) and cats’ (14/82, 17.07%) clinical swabs. The isolates were confirmed biochemically and via VITEK 2 compact system. All isolates showed alpha-type of hemolysis and pigment production. The obtained P. aeruginosa isolates revealed a multidrug resistance pattern by 70.45% in dog isolates while cat isolates demonstrated a higher ratio 78.57%. P. aeruginosa isolates were highly resistant to cephalosporins, trimethoprim/sulfamethoxazole, and intermediate resistant to erythromycin fosfomycin. On the other hand imipenem, amikacin, azithromycin then gentamycin and ciprofloxacin were the most efficient on P. aeruginosa isolates. The study included that P. aeruginosa isolates obtained from canine and feline clinical samples collected from Great Cairo laboratories were characterized by high and intermediate levels of antimicrobial resistance. However, this pattern was directed to some classes of antibiotics, which are not authorized for veterinary use, which could expose an early warning mark and give the need for ongoing monitoring.