Obesity is an important risk factor for sleep disorders. This study aimed to evaluate the association of leptin, zinc and tryptophan (TRP) in obese subjects with sleep deficits [sleep apnea (SA), insomnia (IN)]. In this cross sectional case control, with the verbal and written consent 206, obese with sleep deficits and 30, non-obese/normal identified from various areas of Karachi, Pakistan. The socio-demographic data including; age, body mass index (BMI), education and residence, of participants was collected. After providing informed consent, fasting blood samples were taken and serum was collected. The serum concentration of leptin, zinc and TRP were analyzed by ELISA (Enzyme-linked immunosorbent assay), FAAS (Flame atomic absorption spectrophotometer) and HPLC (High performance liquid chromatography) respectively. A significant correlation was found between BMI (body mass index) and leptin, BMI and zinc, BMI and TRP. The correlation between leptin consecutively was significantly associated with zinc and TRP in obese patients. Sleep deficits elevated circulatory levels of leptin while lower zinc and TRP levels compared to levels seen in non-obese (Normal) subjects with no sleep deficits. Obese subjects exhibited significantly higher levels of leptin with sleep deficits compared with non-obese subjects with normal sleep pattern, while obese subjects with SA had significantly high levels of leptin than obese subjects with IN and IN+SA. Patients with sleep deficits had significantly lower levels of serum TRP and zinc than non-obese subjects with normal sleep pattern. Obese subjects with SA had significantly lower levels of zinc and elevated levels of TRP than obese subjects with IN. Obese patients with IN+SA had significantly lower levels of leptin and zinc than IN and SA , while TRP levels were significantly lower in subjects with IN than obese subjects with IN+SA and IN. These results suggest that elevated levels of leptin which are possibly by adiposity and lessened levels of zinc and TRP have a great impact on progression of obesity and their association can contribute to tempt sleep disorders.