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Simple Summary: Small ruminants fed on cactus pear exclusively in the diet may present nutritional disorders, especially diarrhea. This is due to the high moisture requirements present in this food, related to microbiological factors inherent to poor hygienic quality, such as handling and prolonged exposure of crushed palm to the air, which can cause greater ingestion by animals of certain bacterial groups with pathogenic potential. The aim of this research was to investigate the levels of cactus associated with buffel grass hay on the microbiological quality of diets and the influence on physiological parameters in sheep. Thus, this research revealed that the participation of buffel grass hay was able to reduce the contamination of bacteria that cause diarrhea and depress animal performance. This study aimed to evaluate the microbiological composition of cactus pear-based diets with increasing levels of buffel grass hay, and its effect on the blood and physiological parameters and occurrence of diarrhea in feedlot sheep. Four diets containing different percentages of buffel grass hay were tested. Diets were composed of forage cactus, buffel grass hay and concentrate, and the treatments were represented by different levels of hay in the dry matter of the feed: 7.5% buffel grass hay; 15% buffel grass hay; 30% buffel grass hay; and 45% buffel grass hay on a dry matter basis. There was a significant effect (p = 0.0034) of inclusion levels of buffel grass hay on fecal score. Only at the 45% inclusion level diarrhea was not observed, showing that the level of buffel grass affected more the animals than the collection period, although the collection period has affected the microbial counts. Probably there was a physiological adaptation of animals over time. There were significant changes (p < 0.0001) in the blood parameters of sheep. The reduction of the proportion of cactus and the inclusion of greater than 15% buffel grass hay, on a dry matter basis, provides less contamination of the diet and animal feces by enterobacteria, such as E. coli. [ABSTRACT FROM AUTHOR]