Despite the fact that published evidence on hydrocarbon oxidation is abundant, reports linking preparative isolation procedures to HC oxidation in the open literature are scarce. This paper presents some findings on HC oxidation during isolation of asphaltenes and resins, emphasizing the importance for improved variable control leading to sample degradation. Variables such as sample handling, storage conditions, air and light influence with respect to crude oils, and vacuum residua studies are addressed. Case studies were selected from Venezuela's upstream and downstream historical records and from crude oil production operations in Mexico. Some evidence linking oxygen compound abundance with crude oil intrinsic stability is reviewed.