Due to the results of the COVID-19 epidemic on mental health, some studies have highlighted the positive effects of nature exposure. Nevertheless, this beneficial role has not yet been explored over time of the pandemic. In mid-rise housing, in addition to the small home size, most people do not have access to private outdoor spaces and they use shared open and green areas. It is necessary to understand how household density and nature exposure affect people's mental health in this housing type. The current study examines the longitudinal changes in (a) social isolation, (b) psychological distress, (c) intensity of the effect of social isolation on psychological distress, and (d) moderating effect of nature exposure on the relation between perceived interior crowding, social isolation, and psychological distress. Focusing on six mid-rise housing developments in Mashhad, longitudinal data were collected from 718 middle-aged women (Mage = 49.63, SD = 12.39) in two waves during the Iranian national lockdowns (wave1 in May 2019 and wave2 in April 2020, before nationwide vaccination). A paired-sample t-test showed increased social isolation and psychological distress after one year of the pandemic. Also, using structural equation modeling and multi-group analysis (wave 1 vs. wave 2) revealed that social isolation has an increasing influence on psychological distress over time. Exposure to nature moderates the effect of perceived interior crowding on psychological distress. However, this moderating role is time-dependent and nature exposure during the time did not necessarily assist in reducing the negative impact of perceived interior crowding. Finally, at any given time, nature exposure mitigated the effect of social isolation on psychological distress.