Purpose Despite an acknowledged dearth of data on serum 25-hydroxyvitamin D (25(OH)D) concentrations from Southern European countries, inter-country comparison is hampered by inconsistent data reporting. The purpose of the current study was to conduct a systematic literature review of available data on serum 25(OH)D concentrations and estimate vitamin D status in Southern European and Eastern Mediterranean countries, both at a population level and within key population subgroups, stratified by age, sex, season and country. Methods A systematic review of the literature was conducted to identify and retrieve scientific articles reporting data on serum 25(OH)D concentration and/or vitamin D status following standard procedures. Results Data were extracted from 107 studies, stratified by sex and age group, representing 630,093 individuals. More than one-third of the studies reported mean 25(OH)D concentrations below 50 nmol/L and ~ 10% reported mean serum 25(OH)D concentrations below 25 nmol/L. Overall, females, neonates/ infants and adolescents had the higher prevalence of poor vitamin D status. As expected, there was considerable variability between studies. Specifically, mean 25(OH)D ranged from 6.0 (in Italian centenarians) to 158 nmol/L (in elderly Turkish men); the prevalence of serum 25(OH)D < 50 nmol/L ranged from 6.8 to 97.9% (in Italian neonates). Conclusions Contrary to expectations, there was a high prevalence of low vitamin D status in the Southern Europe and the Eastern Mediterranean regions, despite abundant sunshine. These data further emphasize the need for strategies, such as fortification of foods with vitamin D and/or vitamin D supplementation, which will be tailored to the needs of specific population groups with higher risk of insufficiency or deficiency, to efficiently tackle the pandemic of hypovitaminosis D in Europe.