To understand the changes in crude oil during low-temperature and high-temperature oxidation stages in the development of heavy oil, static oxidation vessels were used to conduct high- and low-temperature oxidation experiments on heavy oil. By utilizing Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analysis technology, the molecular weight and characteristics of oxygen, nitrogen, and sulfur impurity compounds in the crude oil before and after high- and low-temperature oxidation were studied. The results show that the molecular weight distribution characteristics of the crude oil during the low-temperature oxidation stage were similar to those of the original sample, with a distribution range from 200 to 750, presenting a gentle single-peak distribution. During the high-temperature oxidation stage, the molecular weight distribution range was shifted forward, presenting a distinct front peak single-peak distribution. In the impurity compounds containing oxygen, the element was mainly present in the form of noncyclic saturated diacids during the low-temperature oxidation stage. However, during the high-temperature oxidation stage, it was influenced by cyclization, aromatization, and demethylation, accompanied by breakage and aromatization of side chain alkyl and impurity group, resulting in the evolution of impurity compounds in crude oil towards a direction with fewer carbon numbers and lower DBE values. This study explored the relationship between temperature and crude oil structure and composition, which is of great significance for guiding the field development of heavy oil.