A large thoracic spinal cord injury disconnects the hindlimb (HL) sensory-motor cortex from its target, the lumbar spinal cord. The fate of the synaptic structures of the axotomized cortical neurons is not well studied. We evaluated the density of spines on axotomized corticospinal neurons at 3, 7, and 21 days after the injury in adult mice expressing yellow fluorescence protein in a subset of layer 5 neurons. Spine density of the dendritic segment proximal to the soma (in layer 5) declined as early as 3 days after injury, far preceding the onset of somatic atrophy. In the distal segment (in layer 2/3), spine loss was slower and less severe than in the proximal segment. Axotomy of corticospinal axons in the brainstem (pyramidotomy) induced a comparable reduction of spine density, demonstrating that the loss is not restricted to the neurons axotomized in the thoracic spinal cord. Surprisingly, in both forms of injury, the spine density of putative non-axotomized layer 5 neurons was reduced as well. The spine loss may reflect fast rearrangements of cortical circuits after axotomy, for example, by a disconnection of HL cortical neurons from synaptic inputs that no longer provide useful information.