Recently, there has been a growing interest in Cannabis sativa L. (C. sativa) thanks to the legalization of its use for medical and non-medical purposes in some countries. Cannabis sativa plants can produce several compounds of interest called phytocannabinoids, among which Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychoactive constituent of C. sativa, responsible for most of marijuana’s psychological effects, and also has well-known medical properties that can be used to alleviate the symptoms of several diseases. On the other hand, CBD is being increasingly researched for its various alleged health benefits as a food additive. For these reasons, the production and consumption of C. sativa are continuously growing. Pest control is one of the main challenges for the industrial cultivation of C. sativa plants and can be managed with the application of pesticides. Unfortunately, there is still a lack of standards for the use of synthetic pesticides in C. sativa cultures. It is crucial for consumer safety to analyze the nature of the residues of pesticides in C. sativa plants and to understand the metabolic degradation of pesticides by the plants. In this study, C. sativa plants were exposed to five pesticides and then analyzed with high-resolution mass spectrometry (HRMS) to identify the pesticides metabolites. The Precellys Evolution was used to prepare the cannabis leaves samples before LC-HRMS/MS analysis.