Background: Quality sleep is vital for mental function, with its deprivation reducing alertness and impairing concentration. Similarly, a lack of physical activity leads to problematic living and mental health issues such as depression and anxiety. Therefore, the main reason of this study was to solely focus on physiotherapy students and the effect of sleep and physical activity on their mental health. Objective: The research project aimed to observed physical activity and sleep quality in association to mental health among physical therapy students in different universities of Karachi Methods: A cross-sectional study on 360 DPT students in various. Karachi universities was conducted after obtaining approval from the Institute of Physical Medicine and Rehabilitation. The participants, DPT undergraduates aged 18-28 years, were selected through convenient sampling. Exclusion criteria included diagnosed systemic diseases or psychological conditions. The study utilized PSQI, DASS-21, and IPAQ shortform tools. Fisher's exact test was employed to analyse variable associations. Result: The sample's mean age was 21.75 years, Range= 18-28 years. Most (80.60%) were females. Almost all were single (94.90%), and 97.5% were poor sleepers. However, no association was found between sleep quality and depression, anxiety, or stress levels (p values = 0.117, 0.181, 0.293). Conclusion: The study revealed no association was found between poor sleep and physical activity levels with depression, anxiety, and stress in physiotherapy students, even though many face poor sleep. Students with poor sleep quality had higher physical activity levels than those with good sleep quality.