We aimed to evaluate the local and systemic side effects of the COVID-19 vaccine in cancer patients. we conducted a cross-sectional study including cancer patients treated at Habib Bourguiba Hospital in Sfax, Tunisia between January and March 2022. Patients should have received at least 1 dose of a COVID-19 vaccine. We interviewed a total of 106 patients, of which 80.2% were actively treated. Mean age was 52.52. Patients were vaccinated by the Pfizer/BioNTech in 59.8% and the Oxford/AstraZeneca in 22.5%. The most frequent grade 1 or 2 adverse events occurring within 7 days were: pain at injection site (71.7%) and fatigue (38.7%). Only 2 patients developed grade 3 toxicity following vaccination. The most systemic side effects were fatigue (35.8%), fever (25.4%), headache (16.9%) and arthralgia (15.1%). They were more common after the first dose of Oxford/AstraZeneca vaccine compared to the Pfizer/BioNTech vaccine (69.6% vs 42.6%; p = 0.03). Risk of any grade toxicity (local or systemic) following the first dose was correlated with female sex (p = 0.033). Our study showed that systemic side effects were more common after the first dose of Oxford/AstraZeneca vaccine compared to the Pfizer/BioNTech vaccine in cancer patient, with the predominance of any grade of local or systemic toxicity in women.