Abstract The largest mass extinction since the advent of animals occurred during the Permian-Triassic (P-Tr) transition, ca. 252 Ma, and is commonly attributed to the eruption of the Siberian Traps large igneous province. However, the direct killing mechanism is still debated. In this study, we investigated marine redox conditions of the intermediate water column that most organisms inhabit with special attention to the time interval before the onset of the mass extinction. The carbon isotope composition of carbonate and organic carbon (δ13Ccarb and δ13Corg) as well as the nitrogen isotope composition of bulk nitrogen (δ15N) were analyzed in four P-Tr boundary sequences (Zhongli, Jianshi, Ganxi, and Chaotian sections), which record a transect from a shallow water carbonate platform to a deep water, lower ramp slope in South China. δ13Ccarb shows a distinct negative shift in all sections and displays a clear, 2–4‰, decreasing gradient accompanying an increase in water depth both before and after the mass extinction. A distinct negative shift in δ15N is observed in the shallow water Zhongli section, whereas a minor negative shift is present in the three deeper water sections. Before the mass extinction, the δ15N values from shallow water sections are higher than those from deeper waters. The low δ15N values close to 0‰ in deeper water sections suggest that microbial nitrogen fixation was the predominant source of biologically available nitrogen before the onset of the mass extinction. Thus, the water depth- dependent gradient in δ13Ccarb and δ15N suggests that an oxygen-deficient intermediate water column was already present before the mass extinction. The uniform δ15N values around 0‰ accompanying the onset of the mass extinction reveal that anoxic intermediate waters expanded into shallow waters. Meanwhile, the distinct positive shift in δ13Corg observed in upper ramp slope sections, i.e., the Jianshi and Ganxi sections, suggests that a euxinic photic zone was at least episodically present in the earliest Triassic. The temporal coincidence between the expansion of intermediate water column anoxia and the onset of the P-Tr mass extinction supports the hypothesis that marine anoxia was a direct killing mechanism.