In order to investigate whether geochemical, physiographic and lithological differences in two end-member sedimentary settings could evoke varied microbe-sediment interactions, two 25 cm long sediment cores from contrasting regions in the Central Indian Basin have been examined. Site TVBC 26 in the northern siliceous realm (10°S, 75AE5°E) is organic-C rich with 0AE3 ± 0AE09% total organic carbon. Site TVBC 08 in the southern pelagic red clay realm (16°S, 75AE5°E), located on the flank of a seamount in a mid-plate volcanic area with hydrothermal alterations of recent origin, is organic-C poor (0AE1 ± 0AE07%). Significantly higher bacterial viability under anaerobic conditions, generally lower microbial carbon uptake and higher numbers of aerobic sulphur oxidizers at the mottled zones, characterize core TVBC 26. In the carbon-poor environment of core TVBC 08, a doubling of the 14 C uptake, a 250 times increase in the number of autotrophic nitrifiers, a four-fold lowering in the number of aerobic sulphur oxidizers and a higher order of denitrifiers exists when compared with core TVBC 26; this suggests the prevalence of a potentially autotrophic microbial community in core TVBC 08 in response to hydrothermal activity. Microbial activity at the northern TVBC 26 is predominantly heterotrophic with enhanced chemosynthetic activity restricted to tan-green mottled zones. The southern TVBC 08 is autotrophic with increased heterotrophic activity in the deepest layers. Notably, the bacterial activity is generally dependent on the surface productivity in TVBC 26, the carbon-rich core, and mostly independent in TVBC 08, the carbon-poor, hydrothermally influenced core. The northern sediment is more organic sink-controlled and the southern sediment is more hydrothermal source-controlled. Hydrothermal activity and associated rock alteration processes may be more relevant than organic matter delivery in these deep-sea sediments. Thus, this study highlights the relative importance of hydrothermal activity versus organic delivery in evoking different microbial responses in the Central Indian Basin sediments.