Vitamin B₁₂ (VB₁₂) has been reported to degrade PFOS in the presence of Ti^III citrate at 70 °C. Porphyrin-based catalysts have emerged as VB₁₂ analogues and have been successfully used in various fields of research due to their interesting structural and electronic properties. However, there is inadequate information on the use of these porphyrin-based metal complexes in the defluorination of PFOS. We have therefore explored a series of porphyrin-based metal complexes for the degradation of PFOS. Co^II–5,10,15,20-tetraphenyl-21H,23H-porphyrin (Co^II–TPP), Co^II–5,10,15,20-tetrakis(4-methoxyphenyl)-21H,23H-porphyrin (Co^II–M-TPP), and Co^III–M-TPP exhibited efficient reductive defluorination of the branched PFOS. Within 5–8 h, these compounds achieved the same level of PFOS defluorination as VB₁₂ achieved in 7–10 days. For branched isomers, the specific removal rate of the Co^II–TPP–Ti^III citrate system is 64–105 times higher than that for VB₁₂–Ti^III citrate. Moreover, the Co^II–TPP–Ti^III citrate system displayed efficient (51%) defluorination for the branched PFOS (br-PFOS) in 1 day even at room temperature (25 °C). The effects of the iron and cobalt metal centers, reaction pH, and several reductants (NaBH₄, nanosized zerovalent zinc (nZn⁰), and Ti^III citrate) were systematically investigated. Based on the analysis of the products and previously published reports, a new possible defluorination pathway of branched PFOS is also proposed.