In this study we have investigated the efficiency Cobalt (II) (Co(II)) for the activation of sulfite ions following the oxidation of paracetamol used as model contaminants. Physico-chemical parameters that can impact the paracetamol degradation (pH, initial paracetamol concentration, Co(II)/S(IV) molar ratio, oxygen concentration) and contribution of various radicals were investigated in order to elucidate the chemical mechanism. Main results show that the pH is a key factor controlling the efficiency in the system Co(II)/Sulfite. Higher efficiency is observed for pH between 9.0 and 10.0. Increasing S(IV) concentrations, until 1 mM, slightly promoted the degradation of paracetamol. In fact, an excess of sulfite ions inhibits the reaction through the scavenging of SO4− and SO5−. Moreover, degradation efficiency drastically decreases from ∼ 85% to less than 5% in absence of oxygen. SO4− was confirmed to be the main oxidant responsible for the paracetamol degradation. For the first time we determined the second order rate constant between SO4− and paracetamol (1.33 ± 0.79 × 109 M−1 s−1 (at pH 5) and 6.14 ± 0.99 × 108 M−1 s−1 (at pH 11.0)). Moreover, radical-scavenging experiments also suggest the possible implication of SO5−. Hence, this work provides a precise understanding of the overall mechanism and a new promising strategy by using sulfite and transition metal such as Co(II) to promote organic compounds degradation in water under neutral and alkaline pH conditions.