Intravenous drug incompatibilities are a common cause of medical errors, contributing to ineffective therapy and even life-threatening events. The co-administration of drugs must always be supported by studies confirming compatibility and thus guarantee the therapy’s safety. Particular attention should be paid to the possible incompatibilities or degradation of intravenous cephalosporins in different infusion regimens since the administration of drugs with inadequate quality may cause treatment failure. Therefore, an appropriate stability test should be performed. The study aimed to present various aspects of the stability and compatibility of five cephalosporins: cefepime (CFE), cefuroxime (CFU), ceftriaxone (CFX), ceftazidime (CFZ), and cefazoline (CFL). The degradation studies in parenteral infusion fluids and PN admixtures were conducted for CFE and CFU. The interactions between CFX or CFZ and PN admixtures, as well as the compatibility of CFL with five commercial parenteral nutrition (PN) admixtures, were investigated. The content of CFX and CFZ in PN admixture after 24 h was >90%. CFL administered simultaneously with PN admixture by the same infusion set using Y-site was compatible only with Nutriflex Lipid Special. CFE and CFU were stable in all tested infusion fluids for a minimum of 48 h and decomposed in PN admixtures during storage.