Background: The rapid spread of SARS-CoV-2 has elicited an equally rapid development of effective vaccines, leading to a reduction of COVID-19 severity and deaths. There is limited data on COVID-19-related immunity in chronic myeloid leukemia (CML) patients. Methods: SPARTA (SARS2 SeroPrevalence And Respiratory Tract Assessment) is an ongoing observational study for participants age ≥18 years to investigate immunity to SARS-CoV-2 after infection and/or vaccination. We included patients with CML and compared them with a non-cancer group. We collected saliva and peripheral blood to measure antigen levels by RT-PCR and antibodies (secretory IgG antibodies and neutralizing antibodies). Results: From October 1, 2021, to February 4, 2022, we prospectively enrolled 49 participants (23 CML, 26 non-cancer). Most were male (56.5%) in the CML group and female in the control group (61.5%), mean age 56.39 y vs. 51.96 y, respectively, and self-identified as white (87% vs. 76.9%). In the CML group, 11 (47.8%) had ≥1 comorbidities, vs 13 (50%) in the control group. Twenty-one (91.3%) CML patients were receiving tyrosine-kinase inhibitors; 4 (18.2%) non-cancer subjects reported taking any medication. Most participants in both groups had received at least one dose of COVID-19 vaccine (73.9% vs. 73.1%); 100% of CML patients received two doses vs. 84.2% of controls; the CML group had a higher percentage of subjects fully vaccinated (66.7% vs. 25%). The CML group had a lower percentage of patients previously diagnosed with COVID-19 (8.8% vs. 57.7%). However, there was no difference in the detection of SARS-CoV-2 antigen at the time of enrollment (0% vs. 4%). SARS-CoV-2 IgG antibodies were detected in most of the participants regardless of cancer status (78.3% in the CML cohort and 88% in the non-cancer cohort), and neutralizing antibodies were detected in 82.6% and 95.6%, respectively. The two groups had comparable IgG (mean 146.3 Ru/ml vs. 148.9 Ru/ml) and neutralizing (mean 1329.1 ng/ml vs. 1112 ng/ml) antibody levels. Conclusions: Our preliminary data comparing concomitant cohorts with similar socio-demographic characteristics and medical history indicate that a diagnosis of CML did not impact the development of antibodies against SARS-CoV-2. We are conducting continuous analysis of antibodies levels over time to assess the evolution of antibody immunity and functional studies including cellular immunity assessments.