Background: Fructose consumption has been reported to increase the prevalence of obesity, metabolic syndrome and the risk of cardiovascular diseases (CVD). The cardiac autonomic nervous system contributes majorly to cardiovascular physiology and pathology, thus there is need to investigate the impact of fructose intake on this system as it affects cardiac functions. This study, therefore, aims at investigating the effects of acute fructose consumption on cardiac autonomic nerve and autonomic control of cardiac functions. Material and Methods: Twenty rats were grouped equally into control and Fructose (FFR). Fructose (20%w/v) was freely administered via gavage drinking for 2-weeks. Heart rate (HR) and blood pressures were measured using tail cuff blood pressure system. Rats were anesthetized with urethane (1g/kg-i.p.) and cardiac autonomic control assessed through Heart Rate Variability (HRV) using Edan PC ECG. Tyrosine hydroxylase (TH) antibody was used to examine sympathetic nerve in cardiac tissues via immunohistochemistry. Immunoturbidimetry and spectrophotometry were used to evaluate apolipoproteins and oxidative stress markers respectively in serum samples of the rats. Data was subjected to t-test at α0.05. Results: Systolic blood pressure and HR were significantly increased in fructose compared to control (132.4±3.5 vs 117.0±3.0 mmHg, 339.5±8.9 vs 310.0±5.6 bpm, p<0.01). The HRV analysis revealed significantly reduced total power (TP), Low Frequency (LF), High Frequency (HF), RMSSD and SDNN (292.6±1.6, 141.0±9.2, 123.6±9.1, 65.3±0.7, 49.7±1.0 ms2) in fructose compared to control (45,159.3±7839.2, 5434.0±877.0, 19,574.1±4019.1, 107.5±11.5, 72.1±10.9 ms2) with p<0.0001. There was reduced cardiac TH expression in FFR. Apolipoprotein B, Myeloperoxidase, SOD, MDA and Nitric oxide oxidation were significantly (p<0.05) increased while Apolipoprotein A and GSH were reduced significantly (p<0.05) in FFR. Conclusion: Fructose enriched drink caused reduced sympathetic and parasympathetic activities, autonomic imbalance with sympathetic dominance and reduced cardiac tyrosine hydroxylase expression depicting cardiac dysautonomia and denervation. The mechanism for these might be fructose mediated oxidative stress, inflammation and dysapolipoproteinemia.