Background: Serratia marcescenshas emerged as opportunist in increasing number of hospital-associated infections in neonatal intensive care unit (NICUs), particularly as bloodstream infections. It is known to cause outbreaks in the NICUs, with high mortality rate in the vulnerable preterm population. Case presentation: We present a case of one and half month-old preterm neonate who had complaints of intolerance to feeding and failure to thrive. Clinical investigation revealed anaemia and increased inflammatory markers. Blood culture showed growth ofS marcescens.In antimicrobial susceptibility testing, the isolate showed susceptibility to all β-lactams, aminoglycosides and sulfamethoxazole-trimethoprim, but treatment failure occurred with empirical amikacin and piperacillin-tazobactam. Institution of meropenem showed good response. Discussion: In premature babies with very low birth weight along with prolonged NICU stay predisposed them to S marcescens infection. The capacity of S marcescens to resist antibiotic therapy in vivo in spite of the in vitro sensitivity was exemplified in our case. Conclusion: This case study portrays the important feature of S marcescens to develop in-vivo resistance despite being sensitive by in vitro testing which led to therapeutic failure. Carbapenem could be a choice in such treatment failure cases due S marcescens.