Abstract: Background: Central Australia is a vast region of over 1,000,000 km2 that is sparsely populated by about 60,000 people, of whom approximately 40% are Indigenous Australians. The human T-cell lymphotropic virus (HTLV)-1c subtype is endemic to this region, where the Indigenous population is infected with diverse subtype c variants. HTLV-1-associated uveitis has been reported previously with other subtypes, but not HTLV-1c. Case Description: In this case series, we describe the first two cases of uveitis associated with HTLV-1c subtype infection. Uveitis was demonstrated in two Indigenous Central Australian men, one aged 39 y and the other, 48. Both had been referred to the Ophthalmology Department of Alice Springs Hospital, the referral centre for Central Australia, with subacute to chronic loss of visual acuity in their right eyes. Slit lamp examination revealed signs of uveitis. Other causes of uveitis were comprehensively excluded in the first patient and partially in the second, but both had positive HTLV-1 serology and high HTLV-1c proviral loads in peripheral blood. The second patient had an extremely high proviral load of >10% PBL indicating HTLV-1c infection as the most likely cause of uveitis, as proviral loads >1% PBL are associated with an increased risk of HTLV-1-associated inflammatory disease. Both received high-dose corticosteroids, but visual outcomes were poor in each case and they became blind in the affected eyes. They also lived in remote Aboriginal communities and had poor health literacy, complicating therapy and monitoring. Discussion: HTLV-1-associated uveitis is well-described in Japanese and Afro-Caribbean populations, but not in Australia, highlighting the novelty of our series. The HTLV-1c subtype is endemic to Central Australia where prevalence was >40% for Indigenous adults in one remote community. Clinicians should be aware of HTLV-1c infection as a cause of uveitis in Australia (and Melanesia, where HTLV-1c is also endemic), and HTLV-1 serology should be included in the basic uveitis work-up. They should also consider social determinants of health which may affect compliance and follow-up. Conclusion: A coordinated strategy to control the transmission of HTLV-1 among Indgenous Australians, who are generally not informed of the risks associated with this infection, is sorely needed.