Objectives Lower health literacy (HL) is associated with poor outcomes in patients with kidney disease. Since HL matches the patient's competencies with the complexities of the care package, the level of HL sufficient in earlier stages of chronic kidney disease (CKD) may be inadequate for patients with end-stage kidney disease (ESKD) on dialysis. We aimed to analyse the HL profile of patients with ESKD and non-dialysis CKD and examine if there were significant associations with covariates which could be targeted to address HL deficits, thereby improving patient outcomes. Design and setting Cross-sectional study of patients with CKD and ESKD from a single Australian health district. Methods We assessed the HL profile of 114 patients with CKD and 109 patients with ESKD using a 44-item multidomain Health Literacy Questionnaire (HLQ) and examined its association with demographic factors (age, gender, race), smoking, income, education, comorbidities, carer status, cognitive function and depression. Using multivariable logistic regression models, HL profiles of patients with CKD and ESKD were evaluated after adjusting for covariates. Results Patients with ESKD had similar demographics and educational levels compared with patients with CKD. ESKD had significantly higher frequency of vascular disease, cognitive impairment and depression. Patients with ESKD had better HL scores for the social support domain (37.1% vs 19.5% in higher HLQ4 tertile, p=0.004), whereas all other HL domains including engagement with healthcare providers were comparable to CKD. Depression was independently associated with nearly all of the HL domains (HLQ1: OR 2.6, p=0.030; HLQ2: OR 7.9, p=<0.001; HLQ3: OR 7.6, p<0.001; HLQ4: OR 3.5, p=0.010; HLQ5: OR 8.9, p=0.001; HLQ6: OR 3.9, p=0.002; HLQ7: OR 4.8, p=0.001; HLQ8: OR 5.3, p=0.001) and education with HL domains relevant to processing health-related information (HLQ8: OR 2.6, p=0.008; HLQ9: OR 2.5, p=0.006). Conclusions Despite very frequent interactions with health systems, patients with ESKD on dialysis did not have higher HL in engagement with health providers and most other HL domains, compared with patients with CKD. Strategies promoting patient-provider engagement and managing depression which strongly associates with lower HL may address the impact of HL deficits and favourably modify clinical outcomes in renal patients.