Widespread and large populations of the exotic eastern Pacific ophiuroid brittle star Opthiothela mirabilis now occur in southeastern Florida, extending the range of this recently introduced species from southern Brazil northward to the eastern Caribbean Sea and Florida. The Florida brittle stars, representing two lineages, are epibionts on shallow (3-18 m depth), tropical/subtropical plexaurid (e.g., Eunicea spp., Muricea elongata) and gorgoniid (Antillogorgia spp.) octocorals. The scope of this study includes recent distributional records of O. mirabilis in south Florida, field abundances in relation to the cohabiting endemic ctenophore Coeloplana waltoni, behavioral observations of the ophiuroid, ctenophore and the predatory amphipod Caprella penantis, as well as a laboratory experiment testing the effects of the alien ophiuroid on the native ctenophore. Individuals of O. mirabilis have been collected near St. Lucie Inlet, extending its northern-most range by about 110 km since 2019. Two years of field sampling have demonstrated significant declines of the native, benthic ctenophore with increasing abundances of the exotic ophiuroid. Evidence suggests that the ophiuroid is negatively affecting the abundances of the ctenophore through interference competition, greatly aided by its abrasive armature of calcareous spines, plates and hooks. Sporadic and intense predation by a caprellid amphipod (Caprella penantis) also probably contributes to the ctenophore’s decline, but to a lesser extent than that caused by the ophiuroid. Adding to the risk of extinction of C. waltoni is its narrow requirement of living octocorals as hosts and restricted distribution in southeast Florida and the Bahamas.