The COVID-19 pandemic has affected not only public health but also people’s daily lives. Among various strategies to prevent infection, mask wearing and vaccination are considered to be the most effective methods; however, they may affect the comfortable interpersonal distance (IPD) for social interactions. In 2023, although the COVID-19 epidemic is considered to be similar to influenza, the public health sector of Taiwan still plans to give each person at least one dose per year, and even two does for special cases such as the elderly; and more than 90% of Taiwanese are still accustomed to wearing masks in public areas. Compared with mask wearing, studies examining the effects of vaccination on IPD are lacking. Therefore, an online survey was conducted in this study to collect the IPD data of 50 male and 50 female participants to elucidate the effects of mask wearing, vaccination, and target sex variables on IPD. The results showed that all variables significantly affected IPD (allp< 0.001). The effect of masks on IPD (49.1 cm) was slightly greater than that of vaccination (43.5 cm). The IPDs reported for wearing and not wearing masks were 145.7 and 194.8 cm, respectively, and those for vaccinated and unvaccinated were 148.5 and 192.0 cm, respectively. Regardless of participant sex, the IPDs for the female targets were significantly shorter than those for the male targets, which was consistent with the results of previous studies. Although mask wearing and vaccination are functionally different in nature, the findings indicate that the effects of both on IPD are nearly identical, jointly shortening IPD to approximately 93 cm. This implies that not only masks but also vaccination could lead to the shortening of IPD and may cause challenges in the prevention and control of COVID-19 transmission.