Bedding material is a critical component of the mouse environment and affects animal wellbeing and research integrity. Corn cob (CC) bedding has been a common bedding choice in research despite several potential negative aspects of its use. We investigated the use of compressed paper (CP) bedding as a refinement to CC bedding. CP bedding demonstrated greater total and immediate absorption, compared with CC bedding. CP-bedded cages had a reduced frequency of early cage changing prior to the Guide-recommended 2-wk interval for IVC; this reduction was proportional to room census. Intracage ammonia levels were lower in CP-bedded IVC compared with CC-bedded IVC, independent of the age, sex, and number of mice per cage. By contrast, ammonia levels were similar between CP-bedded and CC-bedded static cages. Collectively, these data support the use of CP bedding as a refinement for CC in ventilated mouse cages, in light of increased husbandry efficiency and its positive effect on the welfare of mice.