During the past two decades, the emergence and spread of infectious diseases have caused substantial declines in the biodiversity and abundance of reef-building corals. Despite their increased global prevalence and virulence, little is known about coral diseases on Indian Ocean coral reefs. This study aims to fill this gap in knowledge by identifying the main coral diseases and quantify their prevalence at three localities Reunion, South Africa and Mayotte, determining their spatial distribution and seasonal variation. Principal findings of this study demonstrated the presence of six main coral diseases including black band disease (BBD), white syndromes (WS), pink line syndrome (PLS), growth anomalies (GA), skeleton eroding band (SEB) and Porites white patch syndrome (PWPS). The overall disease prevalence was higher in Reunion (7.5 ± 2.2%; mean ± SE) compared to South Africa (3.9 ± 0.8%; mean ± SE) and Mayotte (2.7 ± 0.3%; mean ± SE). Acropora and Porites were the genera most vulnerable to disease. Spatial variability was detected in both Reunion and South Africa with BBD and WS more prevalent on shallow than deep reefs. There was also evidence of seasonality in two diseases: BBD and WS, their prevalence being higher in summer than winter. Corals exhibiting signs of PWPS revealed extensive tissue fragmentation, generally associated with ovoid basophilic bodies resembling bacterial aggregates within the mesoglea of the body wall. Other organisms, including Cyanobacteria, Nematoda, Ciliata and endophytic algae, were also observed on diseased tissues and were generally associated with the dead epidermis and cell debris. Results of 16S rRNA sequence analysis revealed a high variability between bacterial communities associated with PWPS-infected and healthy tissues in Porites lutea. Several bacterial ribotypes affiliated to potential putative pathogens notably Shimia marina and Vibrio hepatarius were consistently found among the 16S rRNA sequences derived from the PWPS lesions, and absent and/or poorly represented in HT. Primary pathogens involved in the PWPS were also investigated in this study using traditional culturing techniques and laboratory infection trials. Of the 14 isolates selected for the inoculation trials, only the bacterial strain P180R mostly phylogenetically closely related8 to Vibrio tubiashii with its closest known sister taxon, V. hepatarius, was shown to cause signs resembling those of PWPS and satisfied the four Henle-Koch’s postulates. P180R displayed focalised and progressive tissue paling 12 h after inoculation and visible lesions of PWPS were observed 12 h thereafter. Signs of PWPS appeared on 90% of the exposed coral fragments (27 of 30) under controlled environmental conditions. Moreover, the virulence of this marine pathogen was tested and seemed to be strongly dependent on seawater temperature, resulting in significantly higher tissue loss at 30°C than 28°C and 26°C. Finally, a multidisciplinary approach involving field surveys, gross lesion monitoring, histopathology and 454-pyrosequencing was investigated to characterize an atypical form of BBD named PBPS. Histology revealed cyanobacterial penetration of the compromised tissue as well as the presence of basophilic bodies resembling bacterial aggregates in the living tissue, adjacent to the bacterial mat. Bacterial 16S rRNA sequences yielded a broader diversity of bacterial taxa in PBPS-infected tissues than in healthy tissue, represented by the genus Vibrio (24.9%), followed by sulfate-reducers or sulfide-oxidizers such as Desulfovibrio (20%), Clostridium (12.9%) and Arcobacter (9.9%). PBPS appears to be a multi-stage disease triggered by cyanobacterial invasion and resulting in secondary infections by environmental bacteria that grow in mucus-like decomposing tissue.