Objectives: The aim of the study was to describe the prevalence of and examine the factors associated with immunosuppression (CD4<200 cells/μL) among HIV-infected patients attending two large inner London treatment centres. Methods: Patients attending for care who had a CD4 count <200 cells/μL during a 6-month period (1 January to 30 June 2007) were identified from the UK national CD4 surveillance database. Corresponding case notes were reviewed and factors associated with the most recent immunosuppressive episode examined. Patients either previously had a CD4 count >200 cells/μL at any time under follow-up which had decreased (group A) or never had a CD4 count >200 cells/μL (group B; late presenters). Results: Of 4589 patients, 10.2% (467) had at least one CD4 count <200 cells/μL. In group A (60.1% of patients), 70.4% were not receiving antiretroviral therapy (ART) at the time at which the CD4 count fell to <200 cells/μL. Reasons included: treatment interruption (TI; 32.6%), patient declined ART (20.2%), infrequent attendance (19.1%), physician delay in offer (23.1%) and transient CD4 cell count decrease (3.9%). Among those receiving ART, one in three had poor adherence. In group B, 92.3% had started ART after presentation: most had recently started and were responding virologically. AIDS-defining diagnoses occurred in the year preceding the decrease in CD4 cell count in 12.6% of patients in group A and 33.3% of those in group B. Conclusion: The majority of patients became immunosuppressed while under care. Our findings suggest that, in addition to strategies aimed at earlier diagnosis, there are further opportunities to reduce severe immunosuppression in patients already attending for HIV care. © 2009 British HIV Association.