Clostridioides difficile is an anaerobic bacterium that causes ~500,000 gastrointestinal infections each year in the United States, with clinical manifestations ranging from diarrhea to colitis. There are over 15,000 CDI deaths in the U.S., 80% of which occur in patients 65 years or older, which suggests that aging impacts CDI pathogenesis and leads to worse outcomes. Women have also been shown to have an increased risk of CDI. Utilizing a mouse model of CDI, young (2 – 3 months old) and aged (18 – 24 months old) mice were treated with 10 days of cefoperazone and then infected with C. difficile. We found that the initial microbiome had little differences between the sexes, but there were substantial differences in aged vs young mice before antibiotics. After antibiotics and during infection, microbial community structures shifted and showed differences between both sex (male:female) and age (young:old) of the mice. Differences were also found in bacterial groups from fecal and cecal samples in mice with low vs high cecal damage, including decreased Erysipelotrichaceae in low cecal damage young mice. Certain aged mice had low colonization as compared to young mice, with increased Porphyromonadaceae and decreased Lactobacillus. Our talk will discuss these findings examining the impacts of aging and sex on initial microbial community structure and how these communities change during the course of C. difficile infection in mice.