Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by an increased skin cancer risk due to defective repair of ultraviolet (UV)-radiation induced DNA damage. Therefore patients with XP are required to apply stringent sun-protection. Since the skin needs UV-B irradiation for de novo vitamin D synthesis, it has been postulated that sun-protection may lead to a clinically relevant reduction of vitamin D levels. To investigate whether reduced vitamin D levels in XP-patients are caused by the stringent sun-protection measures employed, in this study we examined 15 patients with XP. The 25-hydroxyvitamin (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) serum levels were measured. Additionally, patients received a questionnaire about their sun-protection-behaviour. Serum levels for 25-OHD were decreased in 10 of 15 (67%) patients, however there was no statistically significant association between decreased 25-OHD serum levels and duration of sun-protection (p = 0.84). Results for 1,25-(OH)2D levels showed a probability of < 0.16 and between 0.16 and 0.77 for sun-protection duration of < 20 and 20 to 40 years, respectively (p = 0.0058). There was no statistically significant association between the duration of sun-protection with drometrizole trisiloxane and the probability of reduced 25-OHD and 1,25-(OH)2D levels. In conclusion, this investigation indicates that vitamin D serum levels in patients with XP may be normal, increased or decreased but this is not causally linked to the stringent photoprotective measures carried out in our group of investigated XP-patients.