OBJECTIVE: To assess the safety and feasibility of small volume plasma exchange (SVPE) as an alternative to standard plasma exchange (PE) or intravenous immunoglobulin (IVIg) for Guillain-Barré syndrome (GBS) patients. DESIGN: Non-randomized, single arm, interventional trial. SETTING: National Institute of Neurosciences and Hospital, Dhaka, Bangladesh. PARTICIPANTS: Twenty adult (>18 years) patients with GBS presented within 2 weeks of onset of weakness who were unable to walk unaided for more than 10 meters. INTERVENTIONS: SVPE involves blood cell sedimentation in a blood bag and removal of supernatant plasma after blood cells are re-transfused. This procedure was repeated three to six times a day, for eight consecutive days. OUTCOME MEASURES: Serious adverse events (SAE) were defined as severe sepsis and deep venous thrombosis related to the central vein catheter (CVC) used during SVPE. SVPE was considered safe if less than 5/20 patients experienced a SAE, and feasible if 8 L plasma could be removed within 8 days in at least 15/20 patients. RESULTS Median patient age 33 years (IQR 23-46; range 18-55); 13 (65%) were male. Median MRC sum score was 20 (IQR 0-29; range 0-36); three (15%) patients required mechanical ventilation. One patient developed SAE (severe sepsis, possibly related to CVC). Minor adverse effects were transient hypotension in 10 (50%) patients; CVC-associated bleeding in 10 (50%); transfusion reaction to fresh frozen plasma in 4 (20%); and hypo-albuminemia, anaemia or electrolyte imbalance in 4 (20%). Removal of 8 L plasma was possible in 15 (75%) patients. GBS disability score improved by at least one grade in 14 (70%) patients four weeks after SVPE started. No patients died. CONCLUSION: SVPE seems a safe and feasible alternative treatment to standard PE or IVIg for GBS; further studies of clinical efficacy in low-resource developing countries are warranted. TRIAL REGISTRATION: Clinicaltrials.gov NCT02780570 on May 23, 2016. Strength and limitations of the study: 1. The strength of this study underlies the novel and simple technique of SVPE, which is much less expensive than conventional immunotherapies (plasma exchange and intravenous immunoglobulin). 2. SVPE is corroborated as safe and feasible for the first time in a prospective and standardized cohort of patients with Guillain-Barré syndrome (GBS). 3. The intrinsic limitations of this study are its non-randomized, single arm nature, which is conducted in a single center with a limited sample size of GBS patients. 4. Clinical efficacy of SVPE on patients with GBS was a secondary end-point assessment and therefore deserves a randomized controlled trial in future to assess the clinical efficacy of SVPE for the patients with GBS.