Objective: Malignant Pleural Mesothelioma (MPM) has a poor prognosis and high symptom burden. RESPECT-Meso was a multicenter randomized study examining the role of early specialist palliative care (SPC) on quality of life (QoL) with MPM. This is a post-hoc exploratory analysis of the symptom burden and unmet needs identified from RESPECT-Meso participants. Methods: Exploratory analysis from 174 participants using the General Health Status (GHS) measure (from the EORTC QLQ-C30 QoL questionnaire) and 87 participants using validated assessment questionnaires in those randomized to SPC. Eligibility for the study included confirmed MPM with diagnosis <6 weeks prior, performance score (PS) 0 or 1, no significant physical or psychological comorbidity. Cox proportional hazards models were derived to examine for relationships with survival. Free text was assessed using content analysis, looking for common themes and words. Results: Participants were predominantly male (79.9%), mean age 72.8 years, PS was 0 in 38%, 78% of MPM was epithelioid. At least 3 symptoms were reported in 69.8% of participants, including fatigue (81%), dyspnea (73.3%), pain (61.2%), weight loss (59.3%). Anxiety was reported by 54.7% of participants, 52.3% low mood and 48.8% anhedonia symptoms. After multivariable adjustment, only pain remained statistically significant with a hazard ratio (HR) 2.9 (95% CI 1.3-6.7; p = 0.01). For each 1 unit increase in GHS score, the HR for death was 0.987 (0.978-0.996; p = 0.006), indicating a worse reported QoL is related to shorter survival. Unmet needs were common: 25.9% wanted more information about their condition, 24.7% about their care and 21.2% about their treatment. 79.1% were concerned about the effect of their illness on family. Conclusion: There is a high symptom burden in mesothelioma despite good baseline performance status. A worse QoL is associated with a worse survival. Unmet needs are common, perhaps highlighting a need for improved communication and information sharing.