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Chronic cerebrospinal venous insufficiency (CCSVI) is a condition associated with multiple sclerosis (MS). One mechanism that has been proposed is that the venous obstructions found in MS are due to a chronic persistent venulitis caused by the intra-cellular bacterial parasite, Chlamydophila pneumoniae (Cpn). The objective of the current study is to determine the effect of a combined antibiotic protocol (CAP) on the venous flow in MS patients as measured by a quantitative duplex ultrasound examination (QDUS).A non-randomised before-after cohort study was conducted to investigate differences in blood flow volumes pre and 6-months post antibiotic treatment for Cpn infection. Flow volume data were measured by QDUS across affected and unaffected sides from multiple veins segments, including internal jugular vein (IJV) segments J2 and J3, and vertebral vein (VV), as well as global arterial blood flow (GABF).91 patients were included in the study. 64 (70%) were found to have positive Cpn serology. There was a statistically significant post-treatment difference seen for the affected side of Cpn infected patients (mean difference = 56 mL/min, p = 0.02). There was a non-significant increase seen for the affected side of uninfected patients (mean difference = 23 mL/min, p = 0.2). The difference in these effects (34 mL/min) was not statistically significant (p = 0.3). The mean flow rate decreased in the unaffected side for both infected (−27 mL/min, p = 0.5) and uninfected patients (−69 mL/min, p = 0.01).There was a statistically significant post-treatment increase in GABF for the infected patients (mean difference = 90 mL/min, p = 0.02) and a difference of 76 mL/min for non-infected patients (p = 0.01).A CAP appears to improve the extra-cranial circulation in patients diagnosed with MS. This effect is statistically significant in patients with positive Cpn serology, although patients with negative Cpn serology also show some benefit, betraying a lack of specificity of this effect.