The transition period is the most critical stage in the lactation cycle of dairy cattle. During this period, cows are subjected to high levels of oxidative stress (OS). One way of managing OS is through mineral supplementation with antioxidant micronutrients. The aim of this study was to evaluate the gene expression of transition dairy cows supplemented with the antioxidant trace elements copper (Cu), zinc (Zn), manganese (Mn) and selenium (Se). The study was carried out in a commercial Holstein dairy farm located in General Belgrano, province of Buenos Aires, Argentina. Cows (n = 200) were randomly assigned to either a supplemented or a control group. Blood samples were obtained seven days after calving and used to determine superoxide dismutase (SOD) and glutathione peroxidase activity, antioxidant capacity (AC) and thiobarbituric acid reactive substances. Additionally, RNA-sequencing analysis was performed. The OS index, SOD activity and AC differed significantly between groups, despite only two differentially expressed genes codified for second messengers (adjusted p value < 0.05). This would suggest that trace mineral supplementation of transition dairy cows would not induce changes in gene expression profiles in pathways associated with OS and immune function, since their expression is already high in response to the high OS levels and the dietary changes associated with this period. Nevertheless, considering the role of these minerals as cofactors, a higher availability in the supplemented group would increase antioxidant enzyme activity.