The immune system is a complex and sophisticated network of specialized tissues, organs, cells, proteins, and chemicals which has evolved in order to protect the host from a range of dangerous agents such as bacteria, virus, fungi, and parasites. There is a close relationship between nutritional status and immune function. Hence, immunocompetence can be regarded as a measure of adequate nutrition. Inter-individual variations in many immune functions exist within the normal healthy population and are due to age, genetics, gender, ethnic background, socioeconomic situation, diet, stress, habitual levels of exercise, alcohol consumption, smoking habits, etc. In addition, seasonal and temperature changes as well as being in crowded spaces (e.g., while commuting in public means of transportation, or working in open space offices) pose an additional burden on the immune system. Here we review the literature on the immune supportive properties of vitamins C, D and zinc and the impact of their supplementation in reducing the incidence or ameliorating symptoms of upper respiratory tract infections, which are among the most common infections in humans. Finally, we discuss their relevance in situations known to challenge the immune system such as exposure to temperature changes, to pollutants, or being in crowded spaces which serve as mixers where pathogens can stay suspended and transfer from host to host thereby increasing the risk of spreading infectious diseases because of close contact and long exposure.