Simple SummaryAtopic dermatitis (AD) is a very common allergic skin disease of dogs that is usually accompanied by skin infections, bacterial, fungal, or both. Although treatment of bacterial and fungal infections in dogs with AD has been recommended and is widely practiced, there are only a few studies evaluating its efficacy. The aim of this study was to evaluate the change in the severity of skin lesions and pruritus after the administration of systemic antimicrobials that resulted in the resolution of the infections. In total, 39 dogs were used, and treatment was prescribed according to the laboratory findings. For the evaluation of the skin lesions and pruritus, validated scales were used, and the scores before and after the treatment were compared. The severity of skin lesions and pruritus decreased significantly, by 30% and 35%, respectively. The efficacy of antimicrobial treatment was assessed as good to excellent by the clinician and the owner in 55% and 60% of the dogs, respectively. There was high variability in the response to treatment among dogs and further studies are needed to find factors that can predict the response to antimicrobial treatment in dogs with AD and skin infections.There is a shortage of studies reporting the efficacy of antimicrobial treatment of dogs with atopic dermatitis (AD) and skin infections (SIs). The aim of this study was to evaluate the change in the severity of skin lesions and pruritus, and the overall efficacy of antimicrobial treatment, in dogs with AD and bacterial overgrowth/infection and/or Malassezia dermatitis. A total of 20 dogs with AD and SIs were prospectively enrolled (group A) and they were examined before and after the administration of systemic antimicrobials that resulted in the resolution of SIs. In addition, 19 dogs fulfilling the same inclusion criteria and treated with systemic, with or without topical antimicrobials, were included retrospectively (group B). Since there were no major differences between the groups, their results were combined. The severity of skin lesions decreased significantly, by 30% based on Canine Atopic Dermatitis Extent and Severity Index-4 (CADESI-4), by 28.1% based on the erythema domain of CADESI-4 and based on owner’s global assessment of the severity of skin lesions. Pruritus decreased significantly, by 34.7% based on the Pruritus Visual Analogue Scale (PVAS). The efficacy of antimicrobial treatment was assessed as good to excellent by the investigator and the owner in 55% and 60% of the dogs, respectively. Despite the significant improvement, there was high variability in the response to treatment among dogs. Further studies are needed to find factors that determine the response to antimicrobial treatment in dogs with AD and SIs.