Abstract Background: Repeated arterial puncture is painful. A mathematical method exists for transforming peripheral venous pH, PCO2 and PO2 to arterial eliminating the need for arterial sampling. This study evaluates this method to monitor acid-base and oxygenation during admission for exacerbation of chronic obstructive pulmonary disease (COPD). Methods: Simultaneous arterial and peripheral venous blood was analysed. Venous values were used to calculate arterial pH, PCO2 and PO2, with these compared to measured values using Bland-Altman analysis and scatter plots. Calculated values of PO2 were assessed with previously defined rules. Differences between maximal changes of calculated and measured values were compared using a t-test, with trends analysed by inspection of plots. Results: Fifty-four patients, median age 67 years (range 62-75), were studied on average 3 days. Mean values of pH, PCO2 and PO2 were 7.432±0.047, 6.8±1.7 kPa and 9.2±1.5 kPa, respectively. Calculated and measured arterial pH and PCO2 agreed well, differences having small bias and SD (0.000±0.022 pH, -0.06±0.50 kPa PCO2), significantly better than venous blood alone. Calculated PO2 obeyed the clinical rules. Calculated values could track patients, with no significant differences in maximal changes in measured and calculated values (pH p=0.96, PCO2 p=0.62, PO2 p=0.33), and time-course plots matching quantity and pattern of change in measurements. Conclusions: This study shows that arterial pH, PCO2 and PO2 can be calculated from peripheral venous values so as to characterise changes seen during exacerbation. Application of the method has potential to reduce arterial sampling, decrease discomfort and enable venous sampling as routine practice.