Halogenated phenolic compounds (HPCs) including hydroxylated polychlorobiphenyls (OH-PCBs) and hydroxylated polybromodiphenyl-ethers (OH-PBDEs) can be persistent organic pollutant (POP) metabolites or natural marine compounds. Structurally similar to thyroid hormones (THs), they are retained in blood, transported through selective barriers, and the cause of endocrine and neuronal POP effects. This study presents a meta-analysis of HPC burdens in human and wildlife tissues, including OH-PCBs, OH-PBDEs, Pentachlorophenol, and polybromophenols. HPC blood plasma levels were also compared to known in vitro and in vivo toxicological effect concentrations. Blood, highly perfused, and fetal tissues contained the highest levels of HPCs. Plasma concentrations of analyzed OH-PCBs/PBDEs ranged from 0.1 to 100 nM in humans and up to 240, 454, 800, and 7650 nM for birds, fish, cetaceans, and other mammals, respectively. These concentrations fully fall within the in vitro effect concentrations reported in literature for HPCs of 0.05-10000 nM. We strongly advise further study of HPC blood levels in the general population, children, and fetal tissue to establish background levels and the risk at sensitive development stages. As not all HPCs are, or can be, chemically analyzed, the application of additional bioanalysis might reveal an even greater toxicological relevance of HPCs. In addition, metabolic activation should always be included within in vitro hazard assessment of POPs.