The studies on earthquake loss calculations are typically based on only the mainshock earthquake. As seen in past damaging earthquakes, very often several aftershocks follow the mainshock event. In some cases, these aftershocks further increase the losses in the affected region. In this study, the increase in the expected losses caused by potential aftershock events is investigated for a case study scenario considering Istanbul. A parametric modeling scheme is proposed to systematically modify the vulnerability of buildings depending on the grade of mainshock damage. Subsequently, the aftershock losses were assessed by using these modified vulnerability models. In the results of the study, the expected economic losses and loss of life in the mainshock scenario and different aftershock scenarios are reported. As a result, it was observed that the extent of aftershock-induced losses is sensitive to the location and magnitude of the aftershock. According to the findings of the study, when the effects of aftershocks are taken into account, in terms of economic losses, structural losses increase by 50.6–58% on average, non-structural losses by 69.7–78% and content losses by 3.6–12%. In addition, in terms of loss of life, it increases by 1.25–8.3% on average. Therefore, it is important to consider the potential aftershock-induced losses for reliable evaluation of the expected earthquake losses that may result from damaging earthquake sequences.