Treating and/or preventing clinical mastitis includes administering a cationic steroidal anti-microbial (CSA) formulation to the intra-mammary organ of a mammal (e.g., a dairy cow), such as by injection into the mammary organ and/or topical application. The CSA formulation can be effective in treating and/or preventing mastitis caused by gram positive bacteria, gram negative bacteria, fungus, and/or prototheca. The dairy cow can be lactating and have a somatic cell count (SCC) less than or equal to 500,000 cells/mL at the time of administering the CSA formulation. Alternatively, the dairy cow can be lactating and have a somatic cell count (SCC) greater than 500,000 cells/mL at the time of administering the CSA formulation. The dairy cow can be taken out of production during the administration of the CSA formulation for a period of time of about 3 days or less, 2 days or less, or 1 day or less.