Aim: Serratia marcescens is a bacterial species associated with different types of infections including hospital acquired. The aim of this study was to examine the resistance rates to 3^rd generation cephalosporins and carbapenems in S. marcescens isolates obtained from various clinical samples of patients hospitalized in two Bulgarian University hospitals. Materials and methods: A total of 180 non-duplicate clinically significant isolates of S. marcescens, collected during the period 2017-2021 were examined: blood, n=19; urine, n=64; respiratory tract secretions, n=36; wounds, n=44; others, n=17. Species identification and antimicrobial susceptibility testing were done by Phoenix (BD) and Vitek 2 (bioMerieux) automated systems. Double Disc Synergy Test (DDST) was used as screening test for detection of ESBL (Extended Spectrum Beta-Lactamase) production. Results: A total of 89 isolates (49.4%) were resistant to 3^rd generation cephalosporins. Among these isolates, the DDST was positive in 32.2% (n=58). Isolates, resistant to 3^rd generation cephalosporins were most commonly obtained from patients in Nephrology (n=31), Urology (n=12) аnd ICU (n=12). The highest rate of 3^rd generation cephalosporin resistance was found among the urine isolates (25.6%, n=46), followed by blood (7.2%, n=13) and wound isolates (5%, n=10). In the studied collection of 180 isolates, cefepime resistant were 47.8% (n=86). Three isolates, resistant to 3^rd generation cephalosporins were susceptible to cefepime. Carbapenem resistance in the whole collection was 3.3% (n=6). Conclusion: The high rates of 3^rd generation cephalosporin resistance and ESBL production among clinically significant isolates of S. marcescens and the detection of carbapenem-resistant isolates are worrisome trends, because are associated with infections with very limited treatment alternatives and usually in immunocompromised patients.