Late-onset sepsis (LOS; sepsis occurring after the first 72 h of life) increases the morbidity and mortality of premature neonates, especially those with very low birth weight (≤1,500 g). In LOS, Enterobacter cloacae has been rarely described as a cause of secondary brain abscesses. Our case report summarizes important aspects of cerebral abscesses due to an E. cloacae sepsis in a preterm neonate. Our patient received surgical abscess drainage and rational antibiotic treatment, employing prolonged meropenem infusions plus fosfomycin and subsequent treatment with oral trimethoprim/sulfamethoxazole. Furthermore, we present a review of the current literature from 2009 to 2022, comparing cases similar to our case.