The objective of this study is to identify post SARS-CoV-2 vaccine BNT162b2 (BioNTech & Pfizer) side effects in patients with systemic lupus erythematosus (SLE) at the Cayetano Heredia Hospital, Lima, Peru. A descriptive observational study was designed in patients with SLE at the Immuno-Rheumatology Department of the Cayetano Heredia Hospital, Lima, Peru, immunized with the BNT162b2 vaccine from May 21 to June 30, 2021. Of the total number of patients seen in the service, 100 received the vaccine’s 1st dose, and 90 patients received the 2nd dose; 90% and 92.2% presented symptoms within 10 days after immunization (1st and 2nd doses, respectively), being pain at the inoculation site the most frequent (87%); most of the symptoms presented were of mild intensity. There were 27 episodes of post-immunization flare, 9% and 20% after the 1st and 2nd doses, respectively; the predominant type of flare was articular (85.1%), followed by dermal (18.5%). It was found that a history of renal involvement was associated with the risk of developing flare RR 0.38 (0.15–0.91) and the use of hydroxychloroquine and azathioprine prior to immunization 0.20 (0.06–0.63) and 7.96 (2.70–23.43) respectively. In 100 SLE patients immunized with BNT162b2 vaccine against SARS-CoV-2, 27% of SLE reactivation episodes occurred, two patients were hospitalized for flare severity, and none died.Key Points• Up to 92.2% presented some type of symptom after vaccination, being mostly local and of mild intensity.• Of the population studied, there were 27 episodes of post-vaccination flare, most of which were mild.• In the studied population, taking hydroxychloroquine and having a history of renal disease were associated with a lower risk of presenting post-vaccination flare.