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No, use of hand sanitizer will not weaken your immune system. Follow the directions on the label of hand sanitizers and you will not weaken your immune system. Also, please refer to the second myth in the above discussions on hand hygiene. I am not sure what you mean by "over use". If you use hand sanitizers like you use washing with soap and water there is no chance of weakening the immune system. Remember, if your hands are visibly dirty or soiled wash them with soap and water, dry them, and apply hand sanitizer. If your hands are not visibly dirty or soiled, use a hand sanitizer.