The Seychelles–Chagos Thermocline Ridge (SCTR), is formed by strong air-ocean interactions that cause open-ocean upwelling in the western Indian Ocean (WIO). The SCTR enhances upper-ocean nutrient levels, which promotes phytoplankton growth, leading to high zooplankton abundance and a strong nursery habitat for fish. To evaluate the evidence of significant upwelling in the SCTR, upwelling indicators associated with variability in the mesozooplankton community and other environmental factors were compared between SCTR and non-SCTR regions. We investigated mesozooplankton and physicochemical factors using multiple opening/closing net and environmental sensing system at three epipelagic (0–200 m) depth strata along 67°E (16°S–5°N) in the central and WIO. Survey stations were clustered into six environmental regions, including SCTR regions (I and II) and non-SCTR regions of the Southwest Monsoon Currents (SMC), Cold-Core Eddy (CCE), and the South Equatorial Current regions North(N) and South(S). Higher abundances of mesozooplankton were observed in the surface mixed layer (SML) (mean: 1275 inds. m−3). In the SML, Noctiluca scintillans were distributed ubiquitously, regions in the CCE were significantly different (p < 0.05). The middle layer (ML) of SCTR-II, there were significant peaks (p < 0.05) in abundance (962 inds. m−3) with significantly lower temperatures (mean: 17.7°C), and N. scintillans and Oncaea copepodites were numerically dominant. At the non-SCTR sites in the ML, there were significantly lower abundances, with a dominance of copepodites of Scolecithricella and Scolecithrix. Mesozooplankton abundance (mean: 57 inds. m−3) was significantly variable in the bottom layer (BL). The BL was dominated by either ostracods or Scolecithricella copepodites. Opportunistic copepods such as Oncaea spp. peaked in upwelled waters due to enhanced nutrients and associated high chlorophyll-a concentrations. A principal component analysis of the environmental factors and numerically dominant mesozooplankton groups showed that the dominant groups were affected by significantly elevated temperatures (25.3–29.8°C, p < 0.05) in the SML and by high salinity (34.8–35.7) in the ML. In the BL, there was no significant association between the mesozooplankton groups with any environmental factors. These results suggest the middle layer of the SCTR acts as a hotspot for opportunistic Oncaea spp., and is associated with open-ocean upwelling in the western Indian Ocean.