Disulfide bond reduction occurred now and then during a recombinant protein manufacturing. Their reduction often led in the loss of batches. Various prevention measures were developed. Their implementation in a manufacturing inevitably increases its operation complexity and even might impact its product qualities and process performances. For monoclonal antibody, a decrease in main peak and an increase in acidic peak were observed when air sparging, a reduction prevention measure, was applied during a harvested cell culture fluid (HCCF) hold in the literature (Mun et al., 2015) and in our lab and at-scale manufacturing. The change in the filterability of HCCF was noticed as well in our lab and at-scale manufacturing when air sparging or air overlay was applied. It is highly desirable to apply a reduction measure only if necessary and to apply no strong measure if a moderate one works. The reduction occurrence is determined both by the reduction sensitivity of a recombinant molecule and by the reduction power of HCCF. The reduction power of HCCF varies largely and depends on cells, lysis level, growth stage, and culture conditions. The method of the quantitative risk assessment of disulfide bond reduction was reported here. The quantitative assessment is realized by comparing the reduction sensitivity of a recombinant molecule with the reduction power of its HCCF.