Aim: Minocycline has neuroprotective activities in several models of neurological disorders including spinal cord injury (SCI) where it prevents axonal loss and improves functional recovery. There are still gaps of knowledge on minocycline in SCI including whether it ameliorates neuronal loss at the focal site of trauma, and whether minocycline reduces the activity of matrix metalloproteinases (MMPs), a family of enzymes implicated in the pathophysiology of SCI. This study addressed these gaps. Methods: Mice were treated with either minocycline or vehicle control after a spinal cord contusion. MMPs were compared between the two groups using real time polymerase chain reaction and zymography. Immunohistochemistry was used to examine microglial activation and neuronal cell death. Results: While several MMP members were elevated in the spinal cord following injury, treatment with minocycline did not affect their expression. Importantly, minocycline reduced the loss of neurons in the epicenter of damage to the spinal cord and in segments caudal and rostral to the injury. Conclusion: Despite the inability of minocycline to alter MMPs, the results of neuroprotection at the lesion site support the continued testing of minocycline as a neuroprotective medication in experimental and clinical SCI.