The objective of this study was to explore the relationship between the Perception of Control Scale (PCS) and other measures that incorporate physical disability, optimism, self-efficacy and hopelessness components in a Multiple Sclerosis (MS) sample. One hundred and fifteen participants comprising 44 males and 71 females with a mean age of 45.65 years (standard deviation: 10.43) diagnosed with MS attending the centre for the first time to consult the Rehabilitation Physician, participated in this cohort study. The main outcome measures used were the Expanded Disability Status Scale, the Life Orientation Test (LOT), the Multiple Sclerosis Self-Efficacy Scale (MSSE-control and MSSE-function), the Beck Hopelessness Scale and the PCS. There were at best moderate relationships found between the PCS and the LOT (r = 0.45; P less than 0.01) and the Beck Hopelessness Scale (r = -0.41; P less than 0.01). A weak relationship was found between the PCS and the MSSE-control (r = 0.34; P less than 0.01). There was negligible correlation between the PCS and the MSSE-function (r = 0.15; P less than 0.05) and the Expanded Disability Status Scale (r = -0.15; P greater than 0.05). It can be concluded that Negative perception of control showed an association with decreased optimism, decreased self-efficacy and increased hopelessness in a sample of participants diagnosed with MS. No association was found with perception of control and ambulatory/functional abilities.