Trazodone is an antidepressant agent used in Spain since 1975. There are few documented reports of fatalities solely attributed to trazodone and none in which the main metabolite is analyzed. A fatal case of self-poisoning following oral ingestion is reported along with a description of the validated analytical methods involved, a discussion of poisoning characteristics, and a review of reports describing trazodone overdose cases with analytical results. The deceased was an 86-year-old man with cancer, who suffered depression. He went to see his doctor in a primary health care unit and told him he had just taken an unknown amount of tablets of Deprax to commit suicide. The doctor induced emesis as a first emergency measure. His death occurred before arriving to the hospital, and he left a suicide note nearby. Systematic toxicological analysis of postmortem blood used routinely in our laboratory revealed the presence of trazodone 4.9 mg/L and m-chlorophenyl-piperazine (m-CPP) 0.6 mg/L, its active and major metabolite. In addition, metamizol 19.6 mg/L and 4-methyl-amino-antipyrine (4-MAA) 40.7 mg/L, its active metabolite, were also found in blood. All drugs and metabolites involved in the case were detected using gas chromatography-nitrogen-phosphorus detection (GC-NPD) and confirmed using gas chromatography-mass spectrometry (GC-MS) mode total ion chromatogram. An additional high-performance liquid chromatography-diode array detection (HPLC-DAD) screening also obtained the same results. Quantitation of trazodone together with its metabolite in blood was carried out using GC-NPD, while quantitation of metamizol was performed using HPLC-DAD. Limits of detection for trazodone and m-CPP were 33 and 11 microg/L, respectively, absolute recoveries were more than 86% and 75%, respectively, intra-assay precisions less than 4%, interassay precisions less than 5%, and linearity up to 2.0 mg/L. Limit of detection for metamizol was 1117 microg/L, absolute recovery more than 84%, intra-assay precision less than 8%, interassay precision less than 12%, and linearity up to 48 mg/L. Based on the autopsy findings, patient history, toxicology results, and previously reported trazodone intoxications, the forensic pathologists ruled that the cause of death was due to an overdose of trazodone, and the manner of death was listed as suicide.