Background Olfactory dysfunction is one of the leading symptoms of COVID-19. Previous data suggest a different prevalence between the wild type virus and its subsequent variants. Here, we report on a prospective study to psychophysically compare olfactory function in acute SARS-CoV-2 infection between wild type, VOC alpha and VOC delta. Methods SARS-CoV-2 was confirmed by reverse-transcription quantitative real-time PCR and virus variants were differentiated by high-sensitive next-generation sequencing. Home-quarantined were sent a validated and blinded smell identification test. A detailed instruction ensured correct self-administration. Results A total of 125 patients were included in study. Patients with the wild type of SARS-CoV-2 self-evaluated their olfactory function significant lower on the visual analog score compared patients with the VOCs alpha or delta (4.1 +/- 1.5 vs. 6.8 +/- 2.9 and 7.3 +/- 0.9; p < 0.001). Likewise, a significant difference of the prevalence of psychophysically confirmed hyposmia (wild type: 73%; alpha: 41%; delta 48%; p < 0.01) and smell test score (48 +/- 25% vs. 70 +/- 23% and 67 +/- 18%; p < 0.01) could be seen between wild type on one side and VOCs alpha and delta on the other side. Conclusion In this study, both self-reports and psychophysical testing revealed a significant higher prevalence of olfactory impairment in the wild type of SARS-CoV-2 compared to the VOCs alpha and delta.