The composition and content of asphaltenes in spilled and original wellhead oils from the Deepwater Horizon (DWH) incident provide information on the amount of original oil lost and the processes most responsible for the losses within the first 80 days of the active spill. Spilled oils were collected from open waters, coastal waters and coastal sediments during the incident. Asphaltenes are the most refractory component of crude oils but their alteration in the spilled oils during weathering prevents them from being used directly as a conservative component to calculate original oil losses. The alteration is reflected by their increase in oxygen content and depletion in 12C. Reconnaissance experiments involving evaporation, photo-oxidation, microbial degradation, dissolution, dispersion and burning indicate that the combined effects of photo-oxidation and evaporation are responsible for these compositional changes. Based on measured losses and altered asphaltenes from these experiments, a mean of 61 ± 3 vol% of the original oil was lost from the surface spilled oils during the incident. This mean percentage of original oil loss is considerably larger than previous estimates of evaporative losses based on only gas chromatography (GC) amenable hydrocarbons (32–50 vol%), and highlights the importance of using asphaltenes, as well as GC amenable parameters in evaluating original oil losses and the processes responsible for the losses.