This study explored the effect of mesenchymal stem cells (MSC) conditioned medium (CM) on the severity of systemic inflammatory response caused by acetaminophen administration. The long-term effects of the toxin on the liver tissue were analysed. The effect of a fraction of the conditioned medium on the functional activity of isolated neutrophils was investigated using a model of sterile inflammation. The study showed that the >30 kDa CM fraction possesses the maximum protective effect. Proteins of this fraction reduce the severity of the systemic inflammatory reaction and the extent of liver tissue fibrosis after the toxin injection in the long term. By using the sterile inflammation model, CM was shown to reduce the complex activity of NADPH oxidase, which leads to a decrease in the total reactive oxygen species production. The CM derived from the cultivation of stem cells reduces the severity of the systemic inflammatory response through suppression of the functional activity of neutrophils.