Background: Serotonin known to be a neurotransmitter can regulate several key aspects of liver biology. Aims: This study aimed to determine the role of serum serotonin levels (5-HT) as a non-invasive marker in the prediction of esophageal and fundal varices in cirrhotic patients. Patients and Methods: The study included seventy cirrhotic patients with hepatitis C virus and fifteen apparently healthy subjects as a control group. Patients were further sub-classified according to upper Gastrointestinal Endoscopy into three groups: Group A: Included 30 cirrhotic patients without esophageal varices (OV), Group B: Included 29 cirrhotic patients with OV, Group C: Included 11 cirrhotic patients with OV and fundal varices. All subjects were subjected to full history taking, clinical evaluation, routine laboratory investigations and serum-serotonin by ELISA. Results: The mean level of serum Serotonin showed a gradual increase in cirrhotic patients with the highest level in oesophageal and fundal varices (94.04±8.51ng/ml), followed by patients with oesophagal varices only (39.2±18.38ng/ml), and both groups were significantly increased than the patient group with no oesophageal varices. There was a positive correlation between serum serotonin level and serum creatinine level, presence and grading of oesophagal varices and the presence of fundal varices. Serum serotonin level at a cutoff value 32.2ng/ml had a sensitivity of 72% and a specificity of 60% in prediction of OV in cirrhotic patients but at cutoff level 28.4ng/ml had low sensitivity (55%) and bad specificity (25%) in discrimination between grads of OV, while serum serotonin level at a cutoff value 79.1ng/ml had a sensitivity of 100% and a specificity of 96.6% to diagnose patients with oesophagal and fundal varices. Applying multivariate analysis, serum serotonin level was an independent predictor for oesophagal varices. Conclusion: Serum serotonin levels could be used as a serum non-invasive marker for the presence of gastrooesophageal varices, but it could not discriminate between the grades of oesophageal varices.