Introduction: Melatonin (MLT) is a lypophilic molecule, synthesized in the pineal gland in cyclic periods. It easily enters through the cell membrane by passive difussion and it is possible to detect it in almost any body fluid. It is believed that MLT enteres the saliva by passive diffusion from serum to the salivary glands. Low levels of MLT have been registered in patients with breast cancer, prostate cancer, lung cancer, stomach and colon cancer. One of the possible explanations for this was decreased sleep quality and increased fatigue in cancer patients. Thereby, decreased sleep quality would result in the abberant MLT synthesis during night-time and the overall MLT circadian rhythym. In the last few years, there is a significant improvement in oral cancer (OC) treatment. This is due to the improvement of surgery, radiotherapy and chemotherapy. Nevertheless, a 5 year survival rate has just slightly improved and amounts to 60%. By the information provided by the World Health Organization (WHO), OC is the 8th most common cancer in the world. Aim: The aim of this reserach is to measure MLT in unstimulated whole saliva (UWS), stimulated whole saliva (SWS) and serum. Furthermore, the aim is to assess the sleep quality using the Pittsburgh Sleep Quality Index (PSQI), oral health and infammation status using the Papillary Bleeding Index (PBI) and the correlation of the two with the levels of MLT in saliva and serum. The expected lower levels of MLT in serum and saliva could justify the therapeutic implications of MLT in OC patients. Patients and methods: Only patients with histologically identified oral squamous cell carcinoma were included in this study. Furthermore, only patients with T1N0M0 and T2N0MO cancers, according to the TNM staging, were included in this study. Altogether, 34 patients with OC and 33 sex and age matched patients were included in this study. Saliva and serum was sampled between 7 and 9 a.m. Saliva was sampled using a specially designed saliva collecting apparatus. Saliva stimulation was performed by chewing paraffin blocks. All participants had to meet certain criteria to be included in this study. Detailed medical history was taken before sampling that included the existance of systemic diseases, drug consumption and sleep quality measured by Pittsburgh Sleep Quality Index questionnaire. After sampling, PBI index was used to assess the oral health inflammation status. All samples were tested using ELISA commercialy available kits. Results: The respondents were correctly matched for variables sex and age. Melatonin levels in UWS were significantly higher (P<0.001) in the OC group [median: 3.1 (95% CI: 2.3-4.5)] compared to the control group [median: 0.7 (95% CI: 0.44-1.52)]. Melatonin levels in the SWS were significantly higher (P<0,001) in the experimental group [median: 1.7 (95% CI: 0.9-2.6)] compared to the control group [median: 0.6 (95% CI: 0.1-1.0)]. Serum MLT levels were significantly higher in patients with OC compared to the reference values for serum MLT [median 13,01 (95% CI: 10,08 - 15,14)]. Sleep quality was significantly lower in patients with OC (P = 0.0001, U=249.50), however, due to the higher levels of MLT in serum and saliva, correlation between the PSQI and MLT levels was not established. Using the ROC analysis, MLT showed a sensitivity of 97.1% and specificity of 57.6% as a marker for OC (P<0.0001, AUC = 0.841). A OC predictive model was introduced. Conclusion: Melatonin can be measured in saliva and serum in OC patients. Salivary and serum MLT could present a potential tumour marker for OC. Elevated levels of MLT in serum and saliva could indicate a expression disorder of MLT receptors in OC. To our knowledge, this is the first study measuring MLT in OC patients.