Nosocomial infections caused by Klebsiella pneumoniae and other Gram-negative organisms have emerged as a significant health problem especially in intensive care units (ICU). This study aims to examine K. pneumoniae infections in the ICU of Aseer Central Hospital and to determine their antimicrobial susceptibility and their relationship to patients' clinical outcomes. This is a retrospective observational study done in a tertiary care center in the Aseer region in Saudi Arabia. The study spanned from January 2018 to December 2019. Demographic, microbiologic, and patient outcomes were collected from 276 patients with various infections. Identification of isolates and in vitro susceptibility to 32 antimicrobial agents were done by the Vitek 2 automated system (bioMérieux, Marcy-l'Étoile, France). Prevalence of K. pneumoniae bacteria, their susceptibility to antimicrobials, and effect on clinical outcome were studied. Two hundred seventy-six K. pneumoniae were recovered from ICU patients with various infections. K. pneumoniae isolates (n=276) were collected mainly from the respiratory tract (61%) and K. pneumoniae represented 39% of the major causal agents of ICU infections, followed by Acinetobacter spp. (30%), Pseudomonas aeruginosa (10.0%), Escherichia coli (7%), and others (14%). The mortality among the 276 ICU patients was 33.3%; K. pneumoniae was connected to 42% of the cases and 67% of the total deaths were between 50 and 90 years of age. K. pneumoniae demonstrated high sensitivity and hence can be recommended for in vivo treatment for tigecycline (81%), cefazolin (77.2%), colistin (64.9%), and to a lesser extent norfloxacin (60%) and imipenem (55.5%). High resistance was detected for ampicillin (100%), extended-spectrum β-lactamases-sulbactam (ESBL-SCM) (100%), piperacillin (100%), and ceftazidime (92.5%). Resistance to carbapenems was elevated in ertapenem (65.2%) and meropenem (61.7%). The increase of K. pneumoniae represents a threat to ICU patients, although K. pneumoniae infections were results rather than the causes, as it was connected to almost half of the ICU mortalities. Tigecycline alone or in combination with colistin on high-dose regimens could be a more effective therapy for treating carbapenem-resistant K. pneumoniae infections.