Persistent oxygen-depleted zones in the ocean are known primarily from enclosed basins in temperate regions or the open ocean (including oxygen minimum and limiting zones) (1). However, little is known about the possibility of such zones forming in tropical coastal domains, even though the combination of warmer temperatures and complex geological features in some tropical regions makes their occurrence more likely (1, 2). Here, we report two subsurface oxygen-depleted zones within deep (>490 m) depressions of the Red Sea's Difaht Farasan—a carbonate platform hosting the world's third largest contiguous tropical coral reef system. One zone maintains suboxic oxygen levels (∼11–14 µmol O₂ kg⁻¹), while the other sustains oxygen levels below detection (<2 µmol O₂ kg⁻¹). The suboxic zone shows no fixed nitrogen loss, while the near-anoxic zone hosts anaerobic microbial populations and shows signs of nitrogen loss. We propose that the warm and saline environment of the Red Sea interacts with the semienclosed depressions to restrict vertical mixing, limiting oxygen resupply at depth. However, unlike most other oxygen-depleted zones, our deep-sea vehicle surveys demonstrate that these zones support resistant aerobically respiring taxa, indicating an unusual capacity to reduce aerobic oxygen demands at high temperatures (>21 °C). Targeted exploration of deep tropical coastal environments is crucial for determining whether similar zones exist beyond the Red Sea and understanding their potential responses to climate change.