Background Little is known about quality of life (QOL) at the time of multiple sclerosis (MS) or clinically isolated syndrome (CIS) diagnosis and how it evolves in the critical adjustment period immediately following a new diagnosis. Objectives To (1) describe QOL trajectory in the first year post-MS/CIS diagnosis and (2) examine associations of demographic and biopsychosocial factors with QOL at baseline and as it evolves over the first year post-MS/CIS diagnosis. Methods Participants were N = 250 individuals newly diagnosed with MS or CIS. Participants completed self-report assessments of QOL, demographics, and biopsychosocial factors at 1, 2, 3, 6, 9, and 12 months post-diagnosis using validated measures.Results At 1-month post-diagnosis, QOL M = 75.2/100 with subsequent assessments revealing consistent ratings on average. Modelling revealed a small number of variables that were predictive of QOL at baseline and/or change in QOL over time. Conclusion QOL in the first year post-MS/CIS diagnosis was, on average, high and stable. A subset of modifiable factors across the biopsychosocial spectrum was associated with baseline level of QOL and change in QOL over time. The stability in QOL suggests that patients can be assessed early after diagnosis for key variables that are predictive of both current and future QOL.