Spinal cord trauma causes acute hemorrhage and ischemia, which in turn initiate a cascade of secondary events resulting in cell death and loss of neural tissue at the site of impact. In contusion or compression injuries, the ensuing tissue damage can extend several segments rostral and caudal to the initial insult. Careful quantitative evaluation of the lesion site and measurement of damaged and spared tissue volumes are essential if one is to fully understand the substrates that underlie functional loss and recovery. For example, neuroprotective strategies can improve the sparing of gray and white matter regions that support recovery. Alternatively, reparative strategies may reduce cavitation, alter cellular invasion or tissue contracture, or enhance axonal growth or regeneration. Interpretation of each of these possibilities depends on accurate estimation of the tissue reference volumes. This chapter provides a brief review of the historical context for measuring tissue volumes following spinal cord injury (SCI) in rodent models. Then, procedures are given for determining unbiased estimates of the volume of SCI lesions and spared tissue as well as cellular component volume fractions. The described methods utilize digital images and simple stereological tools that can be applied without sophisticated three-dimensional reconstruction or dedicated stereology software. Finally, the effects of tissue shrinkage on other outcome measures that might be relevant in SCI research studies are discussed.