Purpose Multiple Sclerosis (MS) is a highly variable condition characterised by uncertainty of disease course which can make formation of expectations about the future difficult. This systematic review aimed to examine associations between expectations, or Future Oriented Cognitions (FOCs), and Quality of Life (QOL) in people with MS (PwMS). Methods Following PRISMA guidelines, literature up to October 2019 was searched using Medline, EMBASE, PsycINFO and Web of Science. Quantitative studies that investigated relationships between FOCs and QOL in PwMS (assessed using a standardised QOL assessment) were considered for inclusion. After data extraction, results were analysed using narrative synthesis, focusing on the valence of FOCs (positive, negative, unvalenced). Quality appraisal was conducted using the Mixed Methods Appraisal Tool (MMAT). All stages of the review were patient-led by a person with MS. Results A total of 13 studies met the review inclusion criteria, with a combined sample size of 4,179. Of these studies, 11 involved measures of positive FOCs, most commonly self-efficacy, one measured a negative FOC, with one FOC unclassified. Nine studies found significant associations between QOL and self-efficacy. Although other positively valenced constructs were less frequently reported, significant associations with higher QOL were also evidenced. Conclusions Identifying ways to foster positive FOCs, particularly self-efficacy, may have beneficial effects on QOL. More research is needed to understand the impacts of negative FOCs on QOL to determine whether these processes could be meaningfully targeted in interventions.