Novel synthetic opioids and benzodiazepines are an emerging trend on the narcotic drugs market. We present a lethal case of U-47700 and flubromazepam poisoning. A 24-year-old man suffered apnoea after the consumption of the synthetic opioid U-47700 in combination with the benzodiazepine flubromazepam. After reanimation and hospital admission, hypoxic cerebral damage and severe brain oedema were stated. Six days after admission, mechanical ventilation was discontinued, and the patient died. Seven blood serum samples and one urine sample collected during the hospitalisation were analysed by liquid chromatography-tandem mass spectrometry. In the sample collected 42 minutes after admission, the concentrations of U-47700 and flubromazepam were 370 and 830 ng/mL, respectively. Three days later, the concentrations of U-47700 and flubromazepam dropped to 4.2 and 280 ng/mL, respectively. The resulting concentration-time-curves allowed calculating a U-47700 elimination half-life of approximately six hours and confirmed the previously reported flubromazepam elimination half-life of around 100 hours. In the presented case, intoxication by the synthetic opioid U-47700 with a contribution of flubromazepam can be assumed as the cause of death. The concentration-time curves allow an estimation of the clinical course of similar cases. Flubromazepam may lead to prolonged central-nervous depressant effects.