This mixed-methods study examined longitudinal data, assessing Israeli autistic adults' employment-related changes, resulting from the COVID-19 pandemic. In the quantitative phase, 23 participants answered a survey before and during COVID-19, assessing work-status, mental health, and work-related psychological need satisfaction. The qualitative phase included interviews with ten employed participants. Results indicate a significant decrease in mental health of participants who lost their jobs during COVID-19, while participants who continued to physically attend work, maintained pre-COVID-19 levels on all assessed variables. Participants who transitioned to remote-work from home, showed a marginally significant deterioration in mental health and a significant decrease in satisfaction of work-related psychological needs for competence and autonomy. Qualitative accounts supplement these findings and portray advantages and disadvantages of remote-work. Supplementary Information The online version contains supplementary material available at 10.1007/s10803-021-04902-3.