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Alkylphenols (APs) represent one of the highest exposure levels among endocrine disrupting chemicals (EDCs) in the South China Sea (SCS) due to their extensive use as plastic additives. The concerns about EDCs, including APs, have been reiterated since the surge in plastic waste from the COVID-19 response, but far less is known about the response of AP loadings in the SCS to emerging public policies and activities, including the COVID-19 pandemic. Here, we used cetaceans as bioindicators for monitoring two major APs, 4-nonylphenol (4-NP) and 4-tert-octylphenol (4-t-OP), in nine stranded cetacean species (n = 110) in the SCS between 2004 and 2021. Prior to the COVID-19, APs loads showed decreasing temporal trends for finless porpoises and humpback dolphins, most likely due to China’s restrictions on AP use or a shift in dominant prey species. Unexpectedly, AP loads continued to decline after the COVID-19 outbreak, probably due to a temporal-lag response of marine AP fluxes to the pandemic. The health risk assessments based on hormone biomarkers and toxicity thresholds suggest the potential adverse effects of APs on cetaceans, while recent declines in APs, though limited, may mitigate the detrimental impacts.