BACKGROUND Since December 2020, multiple vaccines have mobilized mass immunization campaigns capable of mitigating the current SARS-COV-2 pandemic. Ad26.COV2.S (JohnsonJohnson/Janssen) is a recombinant, replication-incompetent vector vaccine encoding the SARS-CoV-2 spike (s) protein and is especially protective against severe-critical disease. It is a single-dose injection; adverse effects after vaccine administration are usually mild and self-limited, including pain at the injection site, headache, fatigue, muscle aches, and nausea. Severe adverse events involving hospitalization and death after Ad26.COV2.S rarely occur. However, not unlike previous viral vector vaccines, ongoing clinical trials may unveil rare complications of Ad26.COV2.S. Guillain-Barre Syndrome (GBS) is an autoimmune demyelinating polyneuropathy that can potentially manifest severe neurological symptoms after vaccination. CASE REPORT This report describes a case of classic GBS features that manifested 14 days after a single Ad26.COV2.S vaccine injection. The patient developed flaccid paralysis with treatment-related fluctuations. Our findings warrant further investigation into the potential relationship between SARS-CoV-2 vaccinations and the development of GBS. CONCLUSIONS A temporal association between the Ad26.COV2.S (JohnsonJohnson/Janssen) vaccine and the onset of GBS was demonstrated in this case report. A feasible underlying pathogenic mechanism involves the cross-reactivity of antibodies stimulated by adenovirus vaccine components and peripheral nerve glycoproteins. However, there is currently insufficient evidence to support a causal relationship between Ad26.COV2.S and the development of GBS. Further evidence gathered from clinician surveillance and clinical trials are needed to draw these conclusions.