Background <p>Sickle cell trait (SCT), long believed to be a benign carrier condition, is now being recognized for its association with various health complications. Despite its high prevalence across diverse social groups in India, research on SCT-related comorbidities remains limited. Therefore, this study aims to investigate the health complications associated with SCT among individuals residing in remote areas of Odisha, India.</p> Methods <p>This community-based case-control study was conducted among 382 individuals aged 30 years and above from Scheduled Caste and Scheduled Tribe communities. It comprised 182 individuals with SCT identified through field-based screening (cases) and 200 age-, sex-, and community-matched individuals without SCT (controls). Data on comorbidities were collected through structured interviews, supplemented by available medical records. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate prevalence-based associations between SCT status and reported health conditions.</p> Results <p>SCT individuals reported significantly higher rates of breathing difficulties (23.1%), chronic weakness (34.6%), and common cold (35.7%) compared to controls. Exclusive conditions among SCT individuals included kidney disease, retinopathy, priapism, and hematemesis. Musculoskeletal pain, especially leg pain, was also more common among carriers. Although malaria was historically considered less common in SCT individuals, the present findings show no notable protective effect.</p> Conclusion <p>The study highlights that individuals with SCT experience a higher burden of health problems, suggesting that the trait may not be entirely benign.</p>