Blood cultures are frequently obtained in hospitalized patients with COVID-19, although the diagnostic yield and clinical meaning of culture positivity vary markedly according to case mix, disease severity, and timing of sampling. Omicron-era data remain comparatively limited. We aimed to characterize blood-culture positivity, pathogen distribution, inflammatory correlates, antimicrobial exposure, and short-term outcomes in a homogeneous cohort hospitalized during the SARS-CoV-2 Omicron BA.5 wave. This retrospective observational study included 395 patients hospitalized with SARS-CoV-2 infection between 12 July and 25 September 2022. Patients were categorized as blood-culture positive when a named bacterial species was recorded and as culture negative when “No growth” was documented. Continuous variables were compared using the Mann–Whitney U test and categorical variables using Fisher’s exact or chi-square tests, as appropriate. A parsimonious multivariable logistic regression model was used to explore factors independently associated with blood-culture positivity. Blood cultures were positive in 89/395 patients (22.5%). Gram-positive organisms accounted for 52.8% of positive cultures and Gram-negative organisms for 47.2%. The most frequent isolates were Streptococcus pneumoniae (20.2% of positive cultures), Enterococcus faecalis (18.0%), Klebsiella pneumoniae (18.0%), Staphylococcus aureus (14.6%), Escherichia coli (14.6%), and Pseudomonas aeruginosa (14.6%). Compared with patients with no growth, those with positive cultures had higher admission leukocyte counts (median 13.42 vs. 11.22 × 109/L; p < 0.001), C-reactive protein (116.15 vs. 105.50; p = 0.007), and interleukin-6 (17.24 vs. 9.39; p = 0.027). A documented sepsis diagnosis was more frequent in the culture-positive group (48.3% vs. 28.1%; OR 2.39, 95% CI 1.47–3.88; p < 0.001). Mortality was numerically higher with culture positivity (20.2% vs. 14.4%) but did not reach statistical significance (p = 0.188). In the adjusted model, higher leukocyte count remained independently associated with culture positivity (aOR 1.10 per 1 × 109/L, 95% CI 1.05–1.15; p < 0.001), while vaccination status showed an inverse exploratory association (aOR 0.58, 95% CI 0.35–0.96; p = 0.033). The exploratory model AUC was 0.672 (bootstrap 95% CI 0.608–0.731); calibration was not assessed. Blood-culture positivity was common in this hospitalized BA.5 cohort and showed a nearly balanced Gram-positive/Gram-negative distribution. Leukocytosis and clinically documented sepsis were the clearest correlates of positivity, whereas mortality did not differ significantly. These findings support selective blood-culture use driven by bacterial infection signals and emphasize the need to connect antimicrobial decisions to microbiological evidence.