Vaccination has been one of the most effective public health measures in the history of medicine. However, seemingly inexplicit adverse reactions have been described after the injection of the newer vaccines vs. human papillomavirus (HPV). The symptoms more often reported are chronic pain with paresthesias, headaches, fatigue, and orthostatic intolerance. Adverse reactions appear to be more frequent after HPV vaccination when compared to other type of immunizations. Different isolated cases and small series have described the development of complex regional pain syndrome (CRPS), postural orthostatic tachycardia syndrome (POTS), and fibromyalgia after HPV vaccination. These are illnesses often difficult to diagnose that have overlapping clinical features. Sympathetic nervous system dysfunction seems to play a major role in the pathogenesis of these syndromes. Also, small fiber neuropathy has been recently recognized in CRPS, POTS, and fibromyalgia. This article forwards the hypothesis that small fiber neuropathy and dysautonomia could be the common underlying pathogenesis to the group of rare, but severe reactions that follow HPV vaccination. Clinicians should be aware of the possible association between HPV vaccination and the development of these difficult to diagnose painful dysautonomic syndromes.