Abiraterone acetate is an androgen-receptor pathway inhibitor commonly used for treatment of metastatic prostate cancer. The levels of androgens during treatment with abiraterone acetate with prednisone (AAP) are lower than those achieved by androgen-deprivation therapy only, potentially resulting in a high risk of skeletal muscle loss. The cohort included 43 patients treated with AAP for metastatic hormone-sensitive prostate cancer or metastatic castration-resistant prostate cancer. To detect and quantify sarcopenia, we utilized standard computer tomography (CT) imaging. Skeletal muscle mass index (SMI) was evaluated by assessing two adjacent axial sections at the level of the L3 vertebra. Sarcopenia at the time of AAP initiation was present in 72.1% of patients. Body mass index (BMI) was inversely associated with the presence of sarcopenia at the time of AAP initiation. There was a statistically significant decrease in SMI over AAP treatment. Age > 75 years and the absence of previous radiotherapy were associated with a higher rate of SMI decrease during AAP therapy. Overall and progression-free survival was not significantly associated with SMI decrease during AAP therapy. SMI decline occurs during AAP treatment for mHSPC and mCRPC, and is more pronounced in patients over 75 years old and those without previous local treatment. There was no statistically significant association between survival outcomes and SMI decline during AAP therapy.