Advances in laboratory imaging systems for CT, SPECT, MRI, and PET facilitate routine micro-imaging during pre-clinical investigations. Challenges still arise when dealing with immune-compromised animals, biohazardous agents, and multi-modality imaging. These challenges can be overcome with an appropriate animal management system (AMS), with the capability for supporting and monitoring a rat or mouse during micro-imaging. We report the implementation and assessment of a new AMS system for mice (PRA-3000 / AHS-2750, ASI Instruments, Warren MI), designed to be compatible with a commercial micro-CT / micro-SPECT imaging system (eXplore speCZT, GE Healthcare, London ON). The AMS was assessed under the following criteria: 1) compatibility with the imaging system (i.e. artifact generation, geometric dimensions); 2) compatibility with live animals (i.e. positioning, temperature regulation, anesthetic supply); 3) monitoring capabilities (i.e. rectal temperature, respiratory and cardiac monitoring); 4) stability of co-registration; and 5) containment. Micro-CT scans performed using a standardized live-animal protocol (90 kVp, 40 mA, 900 views, 16 ms per view) exhibited low noise (±19 HU) and acceptable artifact from high-density components within the AMS (e.g. ECG pad contacts). Live mice were imaged repeatedly (with removal and replacement of the AMS) and spatial registration was found to be stable to within ±0.07 mm. All animals tolerated enclosure within the AMS for extended periods (i.e. > one hour) without distress, based on continuous recordings of rectal temperature, ECG waveform and respiratory rate. A sealed AMS system extends the capability of a conventional micro-imaging system to include immune-compromised and biosafety level 2 mouse-imaging protocols.