Background: Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons in the spinal cord, brain stem and motor cortex and has only marginal therapeutic options. Adult stem cells have recently come into the focus of neurological research. While replacement of motor neurons by stem cells currently appears not feasible, there is evidence that non-neuronal cells can be neuroprotective. Objective: Therefore, we evaluated the effects of direct intraspinal administration of human umbilical cord blood cells in a G93A transgenic mouse model of ALS before (day 40) and after symptom onset (day 90). Methods: Treatment effects were assessed by survival analysis, behavioral tests, histological and biochemical analyses. Results: Treatment at early stages increased survival, led to significant improvements in motor performance and significantly reduced motor neuron loss and astrogliosis in the spinal cord. Interestingly females tended to respond better to treatment than males. Conclusion: This study confirms the neuroprotective potential of human umbilical cord blood cells and encourages further investigations.