Objectives The changes in the content of interleukins and complement in the serum of the F1 generation of Fleischer dairy and beef cattle and Holstein cattle (hereinafter referred to as Fuhe F1 cattle) and Holstein cattle (hereinafter referred to as Holstein cattle) under cold stress were studied and the differences in disease resistance between the two types of cattle were compared to provide reference for improving Fleischer cattle and achieving the integrated development of dairy and beef cattle. Methods The experiment with a group design was conducted at two cattle farms in Shihezi City. 30 Fuhe F1 cattle and 30 Holstein cattle including 6 calves, 6 young cattle, 6 mature cattle, 6 mid milk cattle and 6 dry cattle were selected from 400 cattle based on the principle of similar age, parity, and body weight between groups. Interleukin and complement detection kits were used to mainly monitor indexes including interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-6 (IL-6), interleukin-10 (IL-10), complement 3 (C3), complement 4 (C4), etc. Results The average content of IL-2 in the mid milk cattle of Fuhe F1 cattle was 1.12 pg/mL higher than that in Holstein cattle (P<0.05). The average content of IL-3 in the calves, mature cattle and dry cattle of Fuhe F1 cattle was 1.05, 1.51, 0.72 pg/mL higher than that in Holstein cattle (P<0.05). The content of IL-6 in Fuhe F1 cattle were lower than that in Holstein cattle at all stages, but the difference was not significant (P>0.05). The average content of IL-10 in the mature cattle of Fuhe F1 cattle was 2.0 pg/mL higher than that in Holstein cattle (P<0.05). The content of C3 in Fuhe F1 cattle at different stages was 1.26, 1.06, 0.88, 1.09, 2.03 ng/mL higher than that in Holstein cattle (P<0.05). The content of C4 in the young cattle, mature cattle, and dry cattle of Fuhe F1 cattle was 1.38, 2.14, 1.96 ng/mL higher than that in Holstein cattle (P<0.05), respectively. Conclusions Fuhe F1 cattle can stimulate the immune system of the body under cold stress, with strong levels of immune and the ability to adapt to cold environments.