Purpose—To investigate correlation between ocular Demodex infestation and serum. Design—A prospective study to correlate clinical findings with laboratory data. Participants—We consecutively enrolled 59 patients: 34 men and 25 women with a mean age of 60.4±17.6 years (range, 17–93). Methods—Demodex counting was performed based on lash sampling. Serum immunoreactivity to two 62-kDa and 83-kDa proteins derived from B oleronius was determined by Western blot analysis. Facial rosacea, lid margin, and ocular surface inflammation were documented by photography and graded in a masked fashion. Main Outcome Measures—Statistical significance based on correlative analyses of clinical and laboratory data. Results—These 59 patients were age matched, but not gender matched, regarding serum immunoreactivity, ocular Demodex infestation, or facial rosacea. There was a significant correlation between serum immunoreactivity and facial rosacea (P = 0.009), lid margin inflammation (P = 0.040), and ocular Demodex infestation (P = 0.048), but not inferior bulbar conjunctival inflammation (P = 0.573). The Demodex count was significantly higher in patients with positive facial rosacea (6.6±9.0 vs. 1.9±2.2; P = 0.014). There was a significant correlation of facial rosacea with lid margin inflammation (P = 0.016), but not with inferior bulbar conjunctival inflammation (P = 0.728). Ocular Demodex infestation was less prevalent in patients with aqueous tear-deficiency dry eye than those without (7/38 vs. 12/21; P = 0.002). Conclusions—The strong correlation provides a better understanding of comorbidity between Demodex mites and their symbiotic B oleronius in facial rosacea and blepharitis. Treatments directed to both warrant future investigation.