Objective Tuberculosis (TB) is the leading cause of adrenal insufficiency in resource-limited settings. The adrenal gland is the most commonly affected endocrine organ in TB infection. We assessed prevalence and factors associated with functional adrenal insufficiency (FAI) among human immunodeficiency virus (HIV)-infected patients with drug-resistant and drug-susceptible TB in Uganda. Patients with drug-sensitive and -resistant TB were enrolled, examined for clinical signs and symptoms of FAI with an early morning serum cortisol level obtained. FAI was defined as early morning serum cortisol <414 nmol//L. Associations with FAI were modeled using multivariable logistic regression. Results : A total of 311 TB patients were screened, and 272 enrolled. Of these, 117 (43%) had drug-resistant TB. Median age was 32 years (IQR 18-66) and 66% were men. Prevalence of FAI was 59.8%. Mean cortisol levels were lower in participants with drug-resistant than susceptible TB (317.4 versus 488.5 nmol/L; p<0.001 ) . In multivariable analysis, drug-resistant TB (aOR 4.61; 95% CI: 2.3-9.1; p < 0.001), treatment duration > 1month (aOR 2.86 95% CI: 1.4- 5.5; p=0.002) and abdominal pain (aOR 2.06; 95% CI: 1.04-4.09; p=0.038) were significantly associated with FAI. Early morning serum cortisol levels should be quantified in TB-HIV co-infected patients.