Objectives While the use of dual antiretroviral therapies could reduce the toxicity of antiretroviral treatment in treatment‐experienced HIV‐1‐infected patients, it is crucial to know if reducing the number of drugs could lead to an adverse increase in inflammation and activation markers. Methods This was a cross‐sectional pilot study conducted at the HIV‐1 Unit at the Tertiary University Hospital in Madrid, Spain, evaluating biomarkers of activation [interferon‐γ‐induced protein 10 (IP10), high‐sensitivity C‐reactive protein (hs‐CRP), soluble CD14 (sCD14) and sCD163], inflammation [interleukin‐6 (IL‐6)], blood coagulation (d‐dimer), and immune response [interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α and IL‐4] in three groups of suppressed HIV‐1‐infected patients: patients continuing on triple therapy (26 patients), and patients who switched from triple to dual therapy, at 24 or 48 weeks after switching (13 and 36 patients, respectively). Results Demographic and immunovirological parameters were similar in the three groups of patients. IL‐6 and sCD14 levels were lower in patients at 48 weeks after switching to dual therapy compared with those found in patients who continued to receive triple therapy (P = 0.012 and P = 0.001, respectively), with no differences in the levels of the remaining biomarkers. Among patients with nadir CD4 count ≤ 200 cells/μL, sCD14 levels were lower in patients who had been on dual therapy for 48 weeks (14 patients) compared with those found in patients who received ongoing triple therapy (11 patients; P = 0.029), with no differences in the levels of the other biomarkers. Conclusions HIV‐1‐infected patients receiving dual regimens showed similar or even lower levels of inflammatory and activation markers compared with those found in patients who received ongoing triple therapy. Of note, similar data were obtained in patients with low nadir CD4 count.