To investigate the clinical characteristics and systemic risk factors of K. pneumoniae related endogenous endophthalmitis (KPREE) in China and explore the possible pathophysiological mechanisms.This was a retrospective comparative study. All enrolled KPREE patients were followed up for at least 1 month to observe their clinical characteristics, unfavorable prognosis, and risk factors, and were compared with intraocular surgery-related postoperative endophthalmitis (ISRPE).Finally, a total of 15 eyes (3 both eyes) from 12 patients were enrolled in KPREE group, and 11 eyes (none both eyes) from 11 patients were enrolled in ISRPE group. Compared to the ISRPE group, the KPREE group had a higher percentage of fever (100% vs 9.09%, P = 0.000), liver abscess (91.67% vs 0%, P = 0.000), lung involvement (50.00% vs 0%, P = 0.024), and lower plasma albumin levels (24.1 [17.8, 31.7] vs 44.0 [37.7, 48.4], P = 0.001). Furthermore, Pearson's partial correlation analysis showed that fever (adjusted r = 0.592, adjusted P = 0.026) and plasma albumin (adjusted r = -0.658, adjusted P = 0.011) were independent factors associated with KPREE. In the KPREE group, ten eyes received 1-3 intravitreal antibiotic injections within one month. In the ten eyes that underwent injections, due to poor treatment reaction, four eyes experienced evisceration, and two eyes underwent vitrectomy with silicone oil tamponade at 1-month follow-up. And one eye developed sympathetic ophthalmia at 8-month visit.Patients with K. pneumoniae infection with hypoproteinemia or fever should be highly vigilant about the occurrence of KPREE, and more attention should be paid to the contralateral risk of KPREE or sympathetic ophthalmia.