Wild-caught deer mice (Peromyscus maniculatus) may harbor the highly pathogenic Sin Nombre hantavirus. Founding of new colonies of deer mice and use of the species indoors require that they first be shown to be free of the virus. We developed a safe and inexpensive outdoor facility for extended quarantine of deer mice. It consists of 34 self-enclosed artificial burrows (nest boxes) contained within a fenced enclosure (20 by 20 m). The nest box used in this study allowed us to maintain juvenile and adult wild-caught Peromyscus successfully for extended periods (≤18 weeks) through fluctuating weather, including heavy rains, snow, and ambient temperatures of −7.6–41.1°C. Nest boxes were effective for protection against predators, and rodents were unable to escape. Outdoor standards for safe handling of wild hantavirus-infected rodents are applicable in this setting rather than those applying to laboratories intended for high-level biological containment. Use of such enclosures should facilitate the use of deer mice as experimental models in general and allow Peromyscus infected with Sin Nombre virus to be experimentally manipulated outside of a biological containment laboratory.