Abstract Background: Wellness encompasses various interconnected physical, mental, and social dimensions beyond the traditional definition of health. Vitamin D deficiency is a widespread nutritional deficiency, with a prevalence of 80%–90% in India, and is often under-diagnosed and under-treated worldwide. While vitamin D is classically known for its role in bone health, it also has significant extra-skeletal effects, including maintaining muscle function, immunity, anti-inflammatory activity, and cell proliferation and differentiation. Recent studies have linked vitamin D deficiency to fatigue, myalgia, low-energy fractures, muscle weakness, anxiety, and depression. Furthermore, it is implicated in the development of type 1 and type 2 diabetes mellitus (DM) and hypertension. Vitamin D deficiency is also associated with recurrent exacerbations of bronchial asthma, autoimmune diseases, and malignancies. Addressing this deficiency can substantially enhance patient well-being, prevent serious health outcomes, and improve overall wellness. Aim: This study aims to investigate the relationship between wellness and vitamin D levels. Materials and Methods: This prospective nonrandomized therapeutic study was conducted at MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India, and included 246 participants from July 2021 to December 2022. The study included patients reporting generalized weakness, fatigue, myalgia, low mood, lack of motivation, and decreased interest in life by the inclusion and exclusion criteria. Their serum vitamin D levels were tested. Participants with vitamin D deficiency (<30 ng/mL) completed a pre-structured well-being questionnaire and received vitamin D supplementation for 10 weeks. Wellness in these patients was evaluated using a pre-structured post-supplementation well-being questionnaire. Results: The results revealed that out of 324 patients included in the study, 253 (78.1%) were deficient in vitamin D. The highest deficiency rate was among those aged 18–35 years (85.5%). Vitamin D deficiency was more prevalent in females (79.5%, 167 out of 210 females) compared with males (75.4%, 86 out of 114 males). The paired t test results showed a significant increase in post-test vitamin D levels (t = -219.922, P < 0.001) and a significant decrease in post-test Fatigue Assessment Scores (t = 31.328, P < 0.001) and Fatigue Severity Scores (t = 33.066, P < 0.001). Additionally, there was a significant improvement in post-test World Health Organization-Five Well-Being Index (WHO-5) scores (t = -28.495, P < 0.001) and Warwick–Edinburgh Mental Well-being Scores (WEMWBS; t = -28.996, P < 0.001). Karl Pearson’s correlation coefficient indicated that post-supplementation vitamin D levels were positively correlated with post-supplementation Fatigue Assessment Scores (r = 0.315) and Fatigue Severity Scores (r = 0.334). Conversely, they negatively correlated with the WHO-5 Well-being Index (r = -0.322) and the WEMWBS (r = -0.294). Conclusion: This study concludes that wellness is directly correlated with vitamin D levels. There is a significant improvement in the Fatigue Assessment Scale, Fatigue Severity Scale, WHO-5 Well-being Index, WEMWBS, and overall physical, mental, and social wellness following vitamin D supplementation in patients, both with and without comorbidities (hypertension and DM).