The aim was to assess pneumoproteins and a certain biomarker of systemic inflammation in drill floor workers exposed to airborne contaminants generated during drilling offshore, taking into consideration serum biomarkers of smoking, such as nicotine (S-Nico) and cotinine. Blood samples of club cell protein 16 (CC-16), surfactant protein D (SP-D) and C-reactive protein (CRP) were collected before and after a 14-day work period from 65 drill floor workers and 65 referents. Air samples of oil mist, drilling mud components and elemental carbon were collected in person. The drill floor workers were exposed to a median air concentration of 0.18 mg/m³ of oil mist and 0.14 mg/m³ of airborne mud particles. There were no differences in the concentrations of CC-16 and SP-D across the 14-day work period and no difference between drill floor workers and referents at baseline after adjusting for differences in sampling time and smoking. CRP decreased across the work period. There was a strong association between the CC-16 concentrations and the time of sampling. Current smokers with S-Nico > detection limit (DL) had a statistically significantly lower CC-16 concentration, while smokers with S-Nico <DL had CC-16 concentrations similar to that of the non-smokers. Fourteen days of work offshore had no effect on serum pneumoprotein and CRP concentrations. However, the time of blood sampling was observed to have a strong effect on the measured concentrations of CC-16. The effect of current smoking on the CC-16 concentrations appears to be dependent on the S-Nico concentrations.