Neurodegenerative diseases are a leading cause of death worldwide with no cures identified. Thus, there is a critical need for preventative measures and treatments as the number of patients is expected to increase. Many neurodegenerative diseases have sex-biased prevalence, indicating a need to examine sex differences when investigating prevention and treatment strategies. Inflammation is a key contributor to many neurodegenerative diseases and is a promising target for prevention since inflammation increases with age, which is known as inflammaging. Here, we analyzed the protein expression levels of cytokines, chemokines, and inflammasome signaling proteins in the cortex of young and aged male and female mice. Our results show an increase in caspase-1, interleukin (IL)-1β, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and ASC specks in females compared to males. Additionally, there was an increase in IL-1α, VEGF-A, CCL3, CXCL1, CCL4, CCL17, and CCL22 in aging females and an increase in IL-8, IL-17a, IL-7, LT-α, and CCL22 in aging males. IL-12/IL-23p40, CCL13, and IL-10 were increased in females compared to males but not with age. These results indicate that there are sex differences in cortical inflammaging and provide potential targets to attenuate inflammation to prevent the development of neurodegenerative disease.