Abstract: Lambs can often depend mainly on the sheep feeding during breeding. This study aims to investigate the effects of cotton straw (CS) with the different processing treatments on the growth performance, dietary apparent digestibility, and serum biochemical indices of Hu sheep lambs. 45 healthy male Hu sheep lambs around 3 months old were selected in this experiment, with 15 lambs in each group (n=15). The CS was treated in three ways: crushing (FS), micro-storage (WZ), and pelletizing (KL). The raw materials of the experimental diets were the same. The FS and WZ groups were fed with the total mixed ration (TMR). While the KL group was fed with the complete pelleted feed. The experimental results showed that the dry matter intake (DMI) of the KL group was the highest, followed by the FS and WZ groups. The DMI values of the KL group at 60 days were 42.74% and 54.63% higher than that of the FS and WZ groups, respectively (P<0.01). The final body weight of the KL group was extremely significantly higher than that of the FS and WZ group by 17.49% and 15.75%, respectively (P<0.01). The body weight of the KL group at 30 days was 10.52% and 6.13% higher than that of the FS and WZ group, respectively, whereas, the body weight at 60 days was 17.49% and 15.75% higher, respectively (P<0.01). There was no significant difference in the body weight between the FS and WZ groups (P>0.05). Furthermore, the average daily gain (ADG) of the KL group was extremely significantly higher than that of the FS and WZ group by 49.89% and 48.23%, respectively (P<0.01) from day 1 to day 60. There was no significant difference in the apparent digestibility of various nutrients in the diet among the groups (P>0.05). In terms of serum protein metabolism, the content of urea nitrogen in the WZ group was significantly lower than that in the FS and KL group by 19.24% and 12.79%, respectively (P<0.05). The content of alanine aminotransferase in the KL group was significantly higher by 56.47% and 69.33%, respectively (P<0.05). In terms of serum lipid metabolism, the contents of total cholesterol and high-density lipoprotein in the FS group were extremely significantly lower than that in the WZ group by 19.13% (P<0.05) and 23.53% (P<0.01), respectively. The contents of β-hydroxybutyric acid in the FS and WZ groups were extremely significantly lower than that in the KL group by 73.33% and 85.71%, respectively (P<0.01). There was no effect of the three treatments on the apparent digestibility, energy metabolism, and immune indices of sheep. However, there was a significant effect on the protein and lipid metabolism. The pelleted feed of CS significantly improved the production performance of sheep, compared with the crushing and micro-storage treatments. Therefore, the feeding effect of CS feed was greatly varied under different processing. The finding can also provide the theoretical basis for the efficient utilization of CS in the later stage.