PURPOSE: To report two cases of Cellulosimicrobium. spp - A novel cause of endogenous endophthalmitis diagnosed on DNA sequencing. METHODS: Our non-comparative retrospective descriptive case series included two clinically diagnosed cases of endogenous endophthalmitis. We noted the clinical presentations, management outcomes, and microbiological workup. The patients underwent pars plana vitrectomy with intravitreal empirical antibiotics and microbiological investigation of the vitreous sample. The vitreous biopsy samples from both cases underwent routine microbiological evaluation, PCR, and DNA sequencing, which played a crucial role in the diagnosis. RESULTS: Both cases were of young males aged 12 and 13 years, respectively, who presented with painful diminution in vision and redness. The mode of infection was deemed endogenous, given the spontaneous occurrence of endophthalmitis. Both patients underwent pars plana vitrectomy followed by intravitreal empirical antibiotics injection (Vancomycin and Ceftazidime). Vitreous biopsy demonstrated thick Gram-positive beaded bacilli. DNA sequencing revealed Cellulosimicrobium spp. The organism was found to be multi-drug resistant but was susceptible to Vancomycin. Post vitrectomy, a rhegmatogenous retinal detachment was noted. Both patients underwent silicone oil injections and, over the next month, showed complete resolution of endophthalmitis. Snellen's best-corrected visual acuity in Case 1 remained at counting fingers close to face due to a recurrent retinal detachment, while in Case 2, it improved to 20/50 from baseline. CONCLUSION: Cellulosimicrobium spp. can cause endogenous endophthalmitis, and the infection can be multi-drug-resistant. Organism identification may be elusive using routine smear culture techniques but can be confirmed by DNA sequencing.